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Immunopathology and Immunotherapy of Non-Hodgkin Lymphoma

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Cancer Immunology

Abstract

Immunotherapy has been increasingly applied in the treatment of various malignancies in recent decades. Considering the suboptimal results obtained by applying other treatment modalities in the treatment of non-Hodgkin’s lymphoma (NHL), as well as the considerable morbidity posed by the condition, attention has been drawn to immunotherapy as an efficient alternative or complement therapy. In light of the unique immunopathology of NHL, it is recognized as a suitable target for immunotherapy. This chapter seeks to discuss a wide spectrum of immunotherapeutic approaches, ranging from initial monoclonal antibodies (mAbs) to novel techniques developed in recent years, which are still in their infancy. In addition to mAbs as a separate entity, their efficacy in combination with other modalities including chemotherapy and radiotherapy has been provided. Since a clear concept of the pathobiology of NHL would aid in efficient immunotherapy, a brief description with an emphasis on suitable targets for immunotherapy is given before discussing various immunotherapies.

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References

  1. Lunning MA, Vose JM. Management of indolent lymphoma: where are we now and where are we going. Blood Rev. 2012;26(6):279–88.

    PubMed Central  PubMed  Google Scholar 

  2. Czuczman MS, Weaver R, Alkuzweny B, Berlfein J, Grillo-López AJ. Prolonged clinical and molecular remission in patients with low-grade or follicular non-Hodgkin’s lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. J Clin Oncol. 2004;22(23):4711–6.

    CAS  PubMed  Google Scholar 

  3. Robert N, Leyland-Jones B, Asmar L, Belt R, Ilegbodu D, Loesch D, et al. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2–overexpressing metastatic breast cancer. J Clin Oncol. 2006;24(18):2786–92.

    CAS  PubMed  Google Scholar 

  4. Neuberger M, Williams G, Mitchell E, Jouhal S, Flanagan J, Rabbitts T. A hapten-specific chimaeric IgE antibody with human physiological effector function. Nature. 1985;314(6008):268–70.

    CAS  PubMed  Google Scholar 

  5. Foon KA. Immunologic classification of leukemia and lymphoma. Blood. 1986;68(1):1–31.

    CAS  PubMed  Google Scholar 

  6. Ghetie V, Ward ES. Multiple roles for the major histocompatibility complex class I-related receptor FcRn. Annus Rev Immunol. 2000;18(1):739–66.

    CAS  Google Scholar 

  7. Konjevic G, Jurisic V, Jovic V, Vuletic A, Martinovic KM, Radenkovic S, et al. Investigation of NK cell function and their modulation in different malignancies. Immunol Res. 2012;52(1–2):139–56.

    CAS  PubMed  Google Scholar 

  8. Gerber H-P. Emerging immunotherapies targeting CD30 in Hodgkin’s lymphoma. Biochem Pharmacol. 2010;79(11):1544–52.

    CAS  PubMed  Google Scholar 

  9. Carter PJ. Potent antibody therapeutics by design. Nat Rev Immunol. 2006;6(5):343–57.

    CAS  PubMed  Google Scholar 

  10. Jahn T, Zuther M, Friedrichs B, Heuser C, Guhlke S, Abken H, et al. An Il12-Il2-antibody fusion protein targeting Hodgkin’s lymphoma cells potentiates activation of Nk and T cells for an anti-tumor attack. PLoS One. 2012;7(9):e44482.

    PubMed Central  CAS  PubMed  Google Scholar 

  11. Brody J, Levy R. Lymphoma immunotherapy: vaccines, adoptive cell transfer and immunotransplant. Immunotherapy. 2009;1(5):809–24.

    CAS  PubMed  Google Scholar 

  12. Grille S, Moreno M, Brugninib A, Lensb D, Chabalgoity J. A therapeutic vaccine using Salmonella-modified tumor cells combined with interleukin-2 induces enhanced antitumor immunity in B-cell lymphoma. Leuk Res. 2012;37:341–8.

    PubMed  Google Scholar 

  13. van Meerten T, Hagenbeek A. Novel antibodies against follicular non-Hodgkin’s lymphoma. Best Pract Res Clin Haematol. 2011;24(2):231–56.

    PubMed  Google Scholar 

  14. Rimsza LM, Roberts RA, Miller TP, Unger JM, LeBlanc M, Braziel RM, et al. Loss of MHC class II gene and protein expression in diffuse large B-cell lymphoma is related to decreased tumor immunosurveillance and poor patient survival regardless of other prognostic factors: a follow-up study from the Leukemia and Lymphoma Molecular Profiling Project. Blood. 2004;103(11):4251–8.

    CAS  PubMed  Google Scholar 

  15. Miller TP, Lippman SM, Spier CM, Slymen DJ, Grogan TM. HLA-DR (Ia) immune phenotype predicts outcome for patients with diffuse large cell lymphoma. J Clin Invest. 1988;82(1):370.

    PubMed Central  CAS  PubMed  Google Scholar 

  16. Driessens G, Kline J, Gajewski TF. Costimulatory and coinhibitory receptors in anti‐tumor immunity. Immunol Rev. 2009;229(1):126–44.

    PubMed Central  CAS  PubMed  Google Scholar 

  17. Chambers CA. The expanding world of co-stimulation: the two-signal model revisited. Trends Immunol. 2001;22(4):217–23.

    CAS  PubMed  Google Scholar 

  18. Linderoth J, Ehinger M, Jerkeman M, Bendahl P-O, Åkerman M, Berglund M, et al. CD40 expression identifies a prognostic ally favourable subgroup of diffuse large B-cell lymphoma. Leuk Lymph. 2007;48(9):1774–9.

    CAS  Google Scholar 

  19. Stopeck AT, Gessner A, Miller TP, Hersh EM, Johnson CS, Cui H, et al. Loss of B7. 2 (CD86) and intracellular adhesion molecule 1 (CD54) expression is associated with decreased tumor-infiltrating T lymphocytes in diffuse B-cell large-cell lymphoma. Clin Cancer Res. 2000;6(10):3904–9.

    CAS  PubMed  Google Scholar 

  20. Tiemessen MM, Baert MR, Schonewille T, Brugman MH, Famili F, Salvatori DC, et al. The nuclear effector of Wnt-signaling, Tcf1, functions as a T-cell–specific tumor suppressor for development of lymphomas. PLoS Biol. 2012;10(11):e1001430.

    PubMed Central  CAS  PubMed  Google Scholar 

  21. Böckle B, Stanarevic G, Ratzinger G, Sepp N. Analysis of 303 Ro/SS‐A antibody‐positive patients: is this antibody a possible marker for malignancy? Br J Dermatol. 2012;167(5):1067–75.

    PubMed  Google Scholar 

  22. Vera‐Recabarren M, García‐Carrasco M, Ramos‐Casals M, Herrero C. Comparative analysis of subacute cutaneous lupus erythematosus and chronic cutaneous lupus erythematosus: clinical and immunological study of 270 patients. Br J Dermatol. 2010;162(1):91–101.

    PubMed  Google Scholar 

  23. Chiarle R, Podda A, Prolla G, Gong J, Thorbecke GJ, Inghirami G. CD30 in normal and neoplastic cells. Clin Immunol. 1999;90(2):157–64.

    CAS  PubMed  Google Scholar 

  24. Yurchenko M, Sidorenko S. Hodgkin’s lymphoma: the role of cell surface receptors in regulation of tumor cell fate. Exp Oncol. 2010;32(4):214–23.

    CAS  PubMed  Google Scholar 

  25. Zinzani PL, Bendandi M, Martelli M, Falini B, Sabattini E, Amadori S, et al. Anaplastic large-cell lymphoma: clinical and prognostic evaluation of 90 adult patients. J Clin Oncol. 1996;14(3):955–62.

    CAS  PubMed  Google Scholar 

  26. Vega F. Time to look for CD30 expression in diffuse large B cell lymphomas, along the way to immunotherapy. Leuk Lymph. 2013;54:2341–2.

    CAS  Google Scholar 

  27. Borchmann P, Treml JF, Hansen H, Gottstein C, Schnell R, Staak O, et al. The human anti-CD30 antibody 5F11 shows in vitro and in vivo activity against malignant lymphoma. Blood. 2003;102(10):3737–42.

    CAS  PubMed  Google Scholar 

  28. Horn‐Lohrens O, Tiemann M, Lange H, Kobarg J, Hafner M, Hansen H, et al. Shedding of the soluble form of CD30 from the Hodgkin‐analogous cell line L540 is strongly inhibited by a new CD30‐specific antibody (Ki‐4). Int J Cancer. 1995;60(4):539–44.

    PubMed  Google Scholar 

  29. H-J GUSS, DaSilva N, Z-B HU, Uphoff C, Goodwin R, Drexler H. Expression and regulation of CD30 ligand and CD30 in human leukemia-lymphoma cell lines. Leukemia. 1994;8(12):2083–94.

    Google Scholar 

  30. Gruss H, Boiani N, Williams D, Armitage R, Smith C, Goodwin R. Pleiotropic effects of the CD30 ligand on CD30-expressing cells and lymphoma cell lines. Blood. 1994;83(8):2045–56.

    CAS  PubMed  Google Scholar 

  31. Mir SS, Richter BW, Duckett CS. Differential effects of CD30 activation in anaplastic large cell lymphoma and Hodgkin disease cells. Blood. 2000;96(13):4307–12.

    CAS  PubMed  Google Scholar 

  32. Wahl AF, Klussman K, Thompson JD, Chen JH, Francisco LV, Risdon G, et al. The anti-CD30 monoclonal antibody SGN-30 promotes growth arrest and DNA fragmentation in vitro and affects antitumor activity in models of Hodgkin’s disease. Cancer Res. 2002;62(13):3736–42.

    CAS  PubMed  Google Scholar 

  33. Duvic M, Reddy SA, Pinter-Brown L, Korman NJ, Zic J, Kennedy DA, et al. A phase II study of SGN-30 in cutaneous anaplastic large cell lymphoma and related lymphoproliferative disorders. Clin Cancer Res. 2009;15(19):6217–24.

    CAS  PubMed  Google Scholar 

  34. Bartlett NL, Younes A, Carabasi MH, Forero A, Rosenblatt JD, Leonard JP, et al. A phase 1 multidose study of SGN-30 immunotherapy in patients with refractory or recurrent CD30+ hematologic malignancies. Blood. 2008;111(4):1848–54.

    CAS  PubMed  Google Scholar 

  35. Forero‐Torres A, Leonard JP, Younes A, Rosenblatt JD, Brice P, Bartlett NL, et al. A Phase II study of SGN‐30 (anti‐CD30 mAb) in Hodgkin lymphoma or systemic anaplastic large cell lymphoma. Br J Haematol. 2009;146(2):171–9.

    PubMed  Google Scholar 

  36. Tedder TF, Schlossman SF. Phosphorylation of the B1 (CD20) molecule by normal and malignant human B lymphocytes. J Biol Chem. 1988;263(20):10009–15.

    CAS  PubMed  Google Scholar 

  37. van Meerten T, Hagenbeek A, editors. CD20-targeted therapy: the next generation of antibodies. Semin Hematol. 2010;47(2):199–210.

    Google Scholar 

  38. Till BG, Press OW. Treatment of lymphoma with adoptively transferred T cells. Expert Opin Biol Ther. 2009;9(11):1407–25.

    PubMed Central  CAS  PubMed  Google Scholar 

  39. Li H, Ayer LM, Lytton J, Deans JP. Store-operated cation entry mediated by CD20 in membrane rafts. J Biol Chem. 2003;278(43):42427–34.

    CAS  PubMed  Google Scholar 

  40. Cragg MS, Walshe CA, Ivanov AO, Glennie MJ. The biology of CD20 and its potential as a target for mAb therapy. Curr Dir Autoimmun. 2005;8:140–74.

    CAS  PubMed  Google Scholar 

  41. Glennie MJ, French RR, Cragg MS, Taylor RP. Mechanisms of killing by anti-CD20 monoclonal antibodies. Mol Immunol. 2007;44(16):3823–37.

    CAS  PubMed  Google Scholar 

  42. Mössner E, Brünker P, Moser S, Püntener U, Schmidt C, Herter S, et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell–mediated B-cell cytotoxicity. Blood. 2010;115(22):4393–402.

    PubMed Central  PubMed  Google Scholar 

  43. Byrd JC, Kitada S, Flinn IW, Aron JL, Pearson M, Lucas D, et al. The mechanism of tumor cell clearance by rituximab in vivo in patients with B-cell chronic lymphocytic leukemia: evidence of caspase activation and apoptosis induction. Blood. 2002;99(3):1038–43.

    CAS  PubMed  Google Scholar 

  44. Di Gaetano N, Cittera E, Nota R, Vecchi A, Grieco V, Scanziani E, et al. Complement activation determines the therapeutic activity of rituximab in vivo. J Immunol. 2003;171(3):1581–7.

    PubMed  Google Scholar 

  45. Beum PV, Kennedy AD, Williams ME, Lindorfer MA, Taylor RP. The shaving reaction: rituximab/CD20 complexes are removed from mantle cell lymphoma and chronic lymphocytic leukemia cells by THP-1 monocytes. J Immunol. 2006;176(4):2600–9.

    CAS  PubMed  Google Scholar 

  46. Bowles JA, Wang S-Y, Link BK, Allan B, Beuerlein G, Campbell M-A, et al. Anti-CD20 monoclonal antibody with enhanced affinity for CD16 activates NK cells at lower concentrations and more effectively than rituximab. Blood. 2006;108(8):2648–54.

    PubMed Central  CAS  PubMed  Google Scholar 

  47. Koene HR, Kleijer M, Algra J, et al. Fc gammaRIIIa-158V/F polymorphism influences the binding of IgG by natural killer cell Fc gammaRIIIa, independently of the Fc gammaRIIIa-48L/R/H phenotype. Blood. 1997;3(90):1109–14.

    Google Scholar 

  48. Peipp M, van de Winkel JG, Valerius T. Molecular engineering to improve antibodies’ anti-lymphoma activity. Best Pract Res Clin Haematol. 2011;24(2):217–29.

    CAS  PubMed  Google Scholar 

  49. McLaughlin P, Grillo-López AJ, Link BK, Levy R, Czuczman MS, Williams ME, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998;16(8):2825–33.

    CAS  PubMed  Google Scholar 

  50. Maloney DG, Grillo-López AJ, White CA, Bodkin D, Schilder RJ, Neidhart JA, et al. IDEC-C2B8 (rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin’s lymphoma. Blood. 1997;90(6):2188–95.

    CAS  PubMed  Google Scholar 

  51. Cheson BD, Leonard JP. Monoclonal antibody therapy for B-cell non-Hodgkin’s lymphoma. N Engl J Med. 2008;359(6):613–26.

    CAS  PubMed  Google Scholar 

  52. Marcus R, Imrie K, Belch A, Cunningham D, Flores E, Catalano J, et al. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005;105(4):1417–23.

    CAS  PubMed  Google Scholar 

  53. Hosono M, Endo K, Sakahara H, Watanabe Y, Saga T, Nakai T, et al. Human/mouse chimeric antibodies show low reactivity with human anti-murine antibodies (HAMA). Br J Cancer. 1992;65(2):197.

    PubMed Central  CAS  PubMed  Google Scholar 

  54. Chinn P, Braslawsky G, White C, Hanna N. Antibody therapy of non-Hodgkin’s B-cell lymphoma. Cancer Immunol Immunother. 2003;52(5):257–80.

    CAS  PubMed  Google Scholar 

  55. Dahle J, Repetto-Llamazares AH, Mollatt CS, Melhus KB, Bruland ØS, Kolstad A, et al. Evaluating antigen targeting and anti-tumor activity of a new anti-CD37 radioimmunoconjugate against non-Hodgkin’s lymphoma. Anticancer Res. 2013;33(1):85–95.

    CAS  PubMed  Google Scholar 

  56. Ratanatharathorn V, Pavletic S, Uberti JP. Clinical applications of rituximab in allogeneic stem cell transplantation: anti-tumor and immunomodulatory effects. Cancer Treat Rev. 2009;35(8):653–61.

    CAS  PubMed  Google Scholar 

  57. Johnson P, Glennie M, editors. The mechanisms of action of rituximab in the elimination of tumor cells. Semin Oncol. 2003;30(1 Suppl 2):3–8.

    Google Scholar 

  58. Cragg MS, Glennie MJ. Antibody specificity controls in vivo effector mechanisms of anti-CD20 reagents. Blood. 2004;103(7):2738–43.

    CAS  PubMed  Google Scholar 

  59. Maloney DG, Grillo-López AJ, Bodkin DJ, White CA, Liles T-M, Royston I, et al. IDEC-C2B8: results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin’s lymphoma. J Clin Oncol. 1997;15(10):3266–74.

    CAS  PubMed  Google Scholar 

  60. Coiffier B, Lepage E, Brière J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(4):235–42.

    CAS  PubMed  Google Scholar 

  61. Tobinai K, Kobayashi Y, Narabayashi M, Ogura M, Kagami Y, Morishima Y, et al. Feasibility and pharmacokinetic study of a chimeric anti-CD20 monoclonal antibody (IDEC-C2B8, rituximab) in relapsed B-cell lymphoma. Ann Oncol. 1998;9(5):527–34.

    CAS  PubMed  Google Scholar 

  62. Hamaguchi Y, Uchida J, Cain DW, Venturi GM, Poe JC, Haas KM, et al. The peritoneal cavity provides a protective niche for B1 and conventional B lymphocytes during anti-CD20 immunotherapy in mice. J Immunol. 2005;174(7):4389–99.

    CAS  PubMed  Google Scholar 

  63. Uchida J, Hamaguchi Y, Oliver JA, Ravetch JV, Poe JC, Haas KM, et al. The innate mononuclear phagocyte network depletes B lymphocytes through Fc receptor–dependent mechanisms during anti-CD20 antibody immunotherapy. J Exp Med. 2004;199(12):1659–69.

    PubMed Central  CAS  PubMed  Google Scholar 

  64. Gong Q, Ou Q, Ye S, Lee WP, Cornelius J, Diehl L, et al. Importance of cellular microenvironment and circulatory dynamics in B cell immunotherapy. J Immunol. 2005;174(2):817–26.

    CAS  PubMed  Google Scholar 

  65. Maloney D, Liles T, Czerwinski D, Waldichuk C, Rosenberg J, Grillo-Lopez A, et al. Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. Blood. 1994;84(8):2457–66.

    CAS  PubMed  Google Scholar 

  66. Feuring-Buske M, Kneba M, Unterhalt M, Engert A, Gramatzki M, Hiller E, et al. IDEC-C2B8 (rituximab) anti-CD20 antibody treatment in relapsed advanced-stage follicular lymphomas: results of a phase-II study of the German Low-Grade Lymphoma Study Group. Ann Hematol. 2000;79(9):493–500.

    CAS  PubMed  Google Scholar 

  67. Davis T, White C, Grillo-Lopez A, Velasquez W, Link B, Maloney D, et al. Single-agent monoclonal antibody efficacy in bulky non-Hodgkin’s lymphoma: results of a phase II trial of rituximab. J Clin Oncol. 1999;17(6):1851.

    CAS  PubMed  Google Scholar 

  68. Colombat P, Salles G, Brousse N, Eftekhari P, Soubeyran P, Delwail V, et al. Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation. Blood. 2001;97(1):101–6.

    CAS  PubMed  Google Scholar 

  69. Hainsworth JD, Litchy S, Burris HA, Scullin DC, Corso SW, Yardley DA, et al. Rituximab as first-line and maintenance therapy for patients with indolent non-Hodgkin’s lymphoma. J Clin Oncol. 2002;20(20):4261–7.

    CAS  PubMed  Google Scholar 

  70. Ardeseina K, Qian W, Smith P, Warden J, Stevens L, Pocock CF, et al. An intergroup randomised trial of rituximab versus a watch and wait strategy in patients with stage II, III, IV, asymptomatic, non-bulky follicular lymphoma (grades 1, 2 and 3a) a preliminary analysis. Lancet. 2010;15(4):424–35.

    Google Scholar 

  71. Schulz H, Bohlius J, Skoetz N, Trelle S, Kober T, Reiser M, et al. Chemotherapy plus rituximab versus chemotherapy alone for B-cell non-Hodgkin’s lymphoma. Cochrane Database Syst Rev. 2007;4:CD003805.

    PubMed  Google Scholar 

  72. Van Oers MH, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, et al. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin’s lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010;28(17):2853–8.

    PubMed Central  PubMed  Google Scholar 

  73. Salles G, Seymour J, Feugier P, Offner F, Lopez-Guillermo A, Bouabdallah R, et al. Rituximab maintenance for 2 years in patients with untreated high tumor burden follicular lymphoma after response to immunochemotherapy. J Clin Oncol. 2010;28(15S):8004.

    Google Scholar 

  74. van Meerten T, van Rijn RS, Hol S, Hagenbeek A, Ebeling SB. Complement-induced cell death by rituximab depends on CD20 expression level and acts complementary to antibody-dependent cellular cytotoxicity. Clin Cancer Res. 2006;12(13):4027–35.

    PubMed  Google Scholar 

  75. Macor P, Tripodo C, Zorzet S, Piovan E, Bossi F, Marzari R, et al. In vivo targeting of human neutralizing antibodies against CD55 and CD59 to lymphoma cells increases the antitumor activity of rituximab. Cancer Res. 2007;67(21):10556–63.

    CAS  PubMed  Google Scholar 

  76. Wang S-Y, Racila E, Taylor RP, Weiner GJ. NK-cell activation and antibody-dependent cellular cytotoxicity induced by rituximab-coated target cells is inhibited by the C3b component of complement. Blood. 2008;111(3):1456–63.

    PubMed Central  CAS  PubMed  Google Scholar 

  77. Davis TA, Czerwinski DK, Levy R. Therapy of B-cell lymphoma with anti-CD20 antibodies can result in the loss of CD20 antigen expression. Clin Cancer Res. 1999;5(3):611–5.

    CAS  PubMed  Google Scholar 

  78. Burger JA, Ghia P, Rosenwald A, Caligaris-Cappio F. The microenvironment in mature B-cell malignancies: a target for new treatment strategies. Blood. 2009;114(16):3367–75.

    CAS  PubMed  Google Scholar 

  79. Vugmeyster Y, Beyer J, Howell K, Combs D, Fielder P, Yang J, et al. Depletion of B cells by a humanized anti-CD20 antibody PRO70769 in Macaca fascicularis. J Immunother. 2005;28(3):212–9.

    CAS  PubMed  Google Scholar 

  80. Briones J. Emerging therapies for B-cell non-Hodgkin lymphoma. Expert Rev Anticancer Ther. 2009;9(9):1305–16.

    PubMed  Google Scholar 

  81. Cartron G, Dacheux L, Salles G, Solal-Celigny P, Bardos P, Colombat P, et al. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIa gene. Blood. 2002;99(3):754–8.

    CAS  PubMed  Google Scholar 

  82. Weng W-K, Levy R. Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J Clin Oncol. 2003;21(21):3940–7.

    CAS  PubMed  Google Scholar 

  83. Anolik JH, Campbell D, Felgar RE, Young F, Sanz I, Rosenblatt J, et al. The relationship of FcγRIIIa genotype to degree of B cell depletion by rituximab in the treatment of systemic lupus erythematosus. Arthritis Rheum. 2003;48(2):455–9.

    CAS  PubMed  Google Scholar 

  84. Rothe A, Schulz H, Elter T, Engert A, Reiser M. Rituximab monotherapy is effective in patients with poor risk refractory aggressive non-Hodgkin’s lymphoma. Haematologica. 2004;89(7):875–6.

    CAS  PubMed  Google Scholar 

  85. Leonard J, Friedberg J, Younes A, Fisher D, Gordon L, Moore J, et al. A phase I/II study of galiximab (an anti-CD80 monoclonal antibody) in combination with rituximab for relapsed or refractory, follicular lymphoma. Ann Oncol. 2007;18(7):1216–23.

    CAS  PubMed  Google Scholar 

  86. Rule S, Smith P, Johnson PW, Bolam S, Follows GA, Gambell J et al., editors. The addition of rituximab to fludarabine and cyclophosphamide (FC) improves overall survival in newly diagnosed mantle cell lymphoma (MCL): results of the randomised UK National Cancer Research Institute (NCRI) trial. Blood. 2011;118(21):440.

    Google Scholar 

  87. Schulz H, Bohlius JF, Trelle S, Skoetz N, Reiser M, Kober T, et al. Immunochemotherapy with rituximab and overall survival in patients with indolent or mantle cell lymphoma: a systematic review and meta-analysis. J Natl Cancer Inst. 2007;99(9):706–14.

    CAS  PubMed  Google Scholar 

  88. Forstpointner R, Dreyling M, Repp R, Hermann S, Hänel A, Metzner B, et al. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004;104(10):3064–71.

    CAS  PubMed  Google Scholar 

  89. Griffiths R, Mikhael J, Gleeson M, Danese M, Dreyling M. Addition of rituximab to chemotherapy alone as first-line therapy improves overall survival in elderly patients with mantle cell lymphoma. Blood. 2011;118(18):4808–16.

    PubMed Central  CAS  PubMed  Google Scholar 

  90. Martin P, Smith M, Till B. Management of mantle cell lymphoma in the elderly. Best Pract Res Clin Haematol. 2012;25(2):221–31.

    PubMed  Google Scholar 

  91. Heinzelmann F, Ottinger H, Engelhard M, Soekler M, Bamberg M, Weinmann M. Advanced-stage III/IV follicular lymphoma. Strahlenther Onkol. 2010;186(5):247–54.

    PubMed  Google Scholar 

  92. Ghielmini M, Schmitz S-FH, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, et al. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly × 4 schedule. Blood. 2004;103(12):4416–23.

    CAS  PubMed  Google Scholar 

  93. Herold M, Haas A, Srock S, Neser S, Al-Ali KH, Neubauer A, et al. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol. 2007;25(15):1986–92.

    CAS  PubMed  Google Scholar 

  94. Gisselbrecht C. Use of rituximab in diffuse large B‐cell lymphoma in the salvage setting. Br J Haematol. 2008;143(5):607–21.

    CAS  PubMed  Google Scholar 

  95. Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Ferme C, et al. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol. 2005;23(18):4117–26.

    CAS  PubMed  Google Scholar 

  96. Coiffier B, Feugier P, Mounier N, Franchi-Rezgui P, Van Den Neste E, Macro M et al., editors. Long-term results of the GELA study comparing R-CHOP and CHOP chemotherapy in older patients with diffuse large B-cell lymphoma show good survival in poor-risk patients. J Clin Oncol (Meeting Abstracts). 2007;25(18_Suppl):8009.

    Google Scholar 

  97. Kewalramani T, Zelenetz AD, Nimer SD, Portlock C, Straus D, Noy A, et al. Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. Blood. 2004;103(10):3684–8.

    CAS  PubMed  Google Scholar 

  98. Zelenetz A, Hamlin P, Kewalramani T, Yahalom J, Nimer S, Moskowitz C. Ifosfamide, carboplatin, etoposide (ICE)-based second-line chemotherapy for the management of relapsed and refractory aggressive non-Hodgkin’s lymphoma. Ann Oncol. 2002;14:i5–10.

    Google Scholar 

  99. Mey UJ, Orlopp KS, Flieger D, Strehl JW, Ho AD, Hensel M, et al. Dexamethasone, high-dose cytarabine, and cisplatin in combination with rituximab as salvage treatment for patients with relapsed or refractory aggressive non-Hodgkin’s lymphoma. Cancer Invest. 2006;24(6):593–600.

    CAS  PubMed  Google Scholar 

  100. Vellenga E, van Putten WL, van’t Veer MB, Zijlstra JM, Fibbe WE, van Oers MH, et al. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial. Blood. 2008;111(2):537–43.

    CAS  PubMed  Google Scholar 

  101. Corazzelli G, Capobianco G, Arcamone M, Ballerini PF, Iannitto E, Russo F, et al. Long-term results of gemcitabine plus oxaliplatin with and without rituximab as salvage treatment for transplant-ineligible patients with refractory/relapsing B-cell lymphoma. Cancer Chemother Pharmacol. 2009;64(5):907–16.

    CAS  PubMed  Google Scholar 

  102. Rigacci L, Fabbri A, Puccini B, Chitarrelli I, Chiappella A, Vitolo U, et al. Oxaliplatin‐based chemotherapy (dexamethasone, high‐dose cytarabine, and oxaliplatin)±rituximab is an effective salvage regimen in patients with relapsed or refractory lymphoma. Cancer. 2010;116(19):4573–9.

    CAS  PubMed  Google Scholar 

  103. Cabanillas F, Liboy I, Rodriguez-Monge E, Pavia O, Robles N, Maldonado N, et al. A dose dense low toxicity salvage regimen for histologically aggressive non-Hodgkin’s lymphoma (NHL): gemcitabine, rituximab, oxaliplatin combination (GROC) plus pegfilgrastim. J Clin Oncol. 2006;24(June20Suppl):17513.

    Google Scholar 

  104. Nyman H, Adde M, Karjalainen-Lindsberg M-L, Taskinen M, Berglund M, Amini R-M, et al. Prognostic impact of immunohistochemically defined germinal center phenotype in diffuse large B-cell lymphoma patients treated with immunochemotherapy. Blood. 2007;109(11):4930–5.

    CAS  PubMed  Google Scholar 

  105. Chan HC, Hughes D, French RR, Tutt AL, Walshe CA, Teeling JL, et al. CD20-induced lymphoma cell death is independent of both caspases and its redistribution into triton X-100 insoluble membrane rafts. Cancer Res. 2003;63(17):5480–9.

    CAS  PubMed  Google Scholar 

  106. Li B, Zhao L, Guo H, Wang C, Zhang X, Wu L, et al. Characterization of a rituximab variant with potent antitumor activity against rituximab-resistant B-cell lymphoma. Blood. 2009;114(24):5007–15.

    CAS  PubMed  Google Scholar 

  107. Li B, Shi S, Qian W, Zhao L, Zhang D, Hou S, et al. Development of novel tetravalent anti-CD20 antibodies with potent antitumor activity. Cancer Res. 2008;68(7):2400–8.

    CAS  PubMed  Google Scholar 

  108. Davis TA, Grillo-López AJ, White CA, McLaughlin P, Czuczman MS, Link BK, et al. Rituximab anti-CD20 monoclonal antibody therapy in non-Hodgkin’s lymphoma: safety and efficacy of re-treatment. J Clin Oncol. 2000;18(17):3135–43.

    CAS  PubMed  Google Scholar 

  109. Morschhauser F, Marlton P, Vitolo U, Lindén O, Seymour J, Crump M, et al. Results of a phase I/II study of ocrelizumab, a fully humanized anti-CD20 mAb, in patients with relapsed/refractory follicular lymphoma. Ann Oncol. 2010;21(9):1870–6.

    CAS  PubMed  Google Scholar 

  110. Morschhauser F, Leonard JP, Fayad L, Coiffier B, Petillon M-O, Coleman M, et al. Humanized anti-CD20 antibody, veltuzumab, in refractory/recurrent non-Hodgkin’s lymphoma: phase I/II results. J Clin Oncol. 2009;27(20):3346–53.

    CAS  PubMed  Google Scholar 

  111. Hagenbeek A, Gadeberg O, Johnson P, Pedersen LM, Walewski J, Hellmann A, et al. First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial. Blood. 2008;111(12):5486–95.

    CAS  PubMed  Google Scholar 

  112. Teeling JL, Mackus WJ, Wiegman LJ, van den Brakel JH, Beers SA, French RR, et al. The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20. J Immunol. 2006;177(1):362–71.

    CAS  PubMed  Google Scholar 

  113. Bowles JA, Weiner GJ. CD16 polymorphisms and NK activation induced by monoclonal antibody-coated target cells. J Immunol Methods. 2005;304(1):88–99.

    CAS  PubMed  Google Scholar 

  114. Barth M, Hernandez-Ilizaliturri F, Mavis C, Tsai P, Gibbs J, Czuczman M, editors. Activity of ofatumumab (OFA), a fully human monoclonal antibody targeting CD20, against rituximab (RTX)-sensitive (RSCL) and rituximab-resistant cell lines (RRCL), in vivo, and primary tumor cells derived from patients with B-cell lymphoma. J Clin Oncol (Meeting Abstracts). 2010;28(15):8095.

    Google Scholar 

  115. Hagenbeek A, Fayad L, Delwail V, Rossi JF, Jacobsen E, Kuliczkowski K et al., editors. Evaluation of ofatumumab, a novel human CD20 monoclonal antibody, as single agent therapy in rituximab-refractory follicular lymphoma. Blood. 2009;114(22):385–6.

    Google Scholar 

  116. Czuczman M, Viardot A, Hess G, Gadeberg O, Pedersen L, Gupta I, et al. Ofatumumab combined with CHOP in previously untreated patients with follicular lymphoma (FL). J Clin Oncol. 2010;28(15):8042.

    Google Scholar 

  117. Sharkey RM, Press OW, Goldenberg DM. A re-examination of radioimmunotherapy in the treatment of non-Hodgkin lymphoma: prospects for dual-targeted antibody/radioantibody therapy. Blood. 2009;113(17):3891–5.

    PubMed Central  CAS  PubMed  Google Scholar 

  118. Beers SA, Chan CH, James S, French RR, Attfield KE, Brennan CM, et al. Type II (tositumomab) anti-CD20 monoclonal antibody out performs type I (rituximab-like) reagents in B-cell depletion regardless of complement activation. Blood. 2008;112(10):4170–7.

    CAS  PubMed  Google Scholar 

  119. Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, et al. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011;377(9759):42–51.

    CAS  PubMed  Google Scholar 

  120. Goldenberg DM, Rossi EA, Stein R, Cardillo TM, Czuczman MS, Hernandez-Ilizaliturri FJ, et al. Properties and structure-function relationships of veltuzumab (hA20), a humanized anti-CD20 monoclonal antibody. Blood. 2009;113(5):1062–70.

    PubMed Central  CAS  PubMed  Google Scholar 

  121. Negrea OG, Allen SL, Rai KR, Elstrom R, Abassi R, Farber CM et al., editors. Subcutaneous injections of low doses of humanized anti-CD20 veltuzumab for treatment of indolent B-cell malignancies. Blood. 2009;114(22):1446.

    Google Scholar 

  122. Rossi EA, Goldenberg DM, Cardillo TM, Stein R, Wang Y, Chang C-H. Novel designs of multivalent anti-CD20 humanized antibodies as improved lymphoma therapeutics. Cancer Res. 2008;68(20):8384–92.

    CAS  PubMed  Google Scholar 

  123. Morschhauser F, Marlton P, Vitolo U, Linden O, Seymour J, Crump M et al., editors. Interim results of a phase I/II study of ocrelizumab, a new humanised anti-CD20 antibody in patients with relapsed/refractory follicular non-Hodgkin’s lymphoma. Blood. 2007;110(11):199A.

    Google Scholar 

  124. Maloney DG. Follicular NHL: from antibodies and vaccines to graft-versus-lymphoma effects. ASH Educ Program Book. 2007;2007(1):226–32.

    Google Scholar 

  125. Bello C, Sotomayor EM. Monoclonal antibodies for B-cell lymphomas: rituximab and beyond. ASH Educ Program Book. 2007;2007(1):233–42.

    Google Scholar 

  126. Friedberg JW, Vose JM, Kahl BS, Brunvand MW, Goy A, Kasamon YL et al., editors. A phase I study of PRO131921, a novel anti-CD20 monoclonal antibody in patients with relapsed/refractory CD20 (+) indolent NHL: correlation between clinical responses and AUC pharmacokinetics. Blood. 2009;114(22):3742.

    Google Scholar 

  127. Salles G, Morschhauser F, Lamy T, Milpied N, Thieblemont C, Tilly H et al., editors. Phase I study of RO5072759 (GA101) in patients with relapsed/refractory CD20+ non-Hodgkin lymphoma (NHL). Blood. 2009;114(22):169.

    Google Scholar 

  128. Sehn LH, Assouline SE, Stewart DA, Mangel J, Pisa P, Kothari J et al., editors. A phase I study of GA101 (RO5072759) monotherapy followed by maintenance in patients with multiply relapsed/refractory CD20 (+) malignant disease. Blood. 2009;114(22):285.

    Google Scholar 

  129. Salles A, Morschhauser F, Thieblemont C, Solal-Celigny P, Lamy T, Tilly H, et al. Promising efficacy with the new anti-CD20 antibody GA101 in heavily pre-treated patients-first results from a phase II study in patients with relapsed/refractory indolent NHL (INHL). Haematologica. 2010;95 suppl 2:229.

    Google Scholar 

  130. Hayden-Ledbetter MS, Cerveny CG, Espling E, Brady WA, Grosmaire LS, Tan P, et al. CD20-directed small modular immunopharmaceutical, TRU-015, depletes normal and malignant B cells. Clin Cancer Res. 2009;15(8):2739–46.

    CAS  PubMed  Google Scholar 

  131. Sgroi D, Varki A, Braesch-Andersen S, Stamenkovic I. CD22, a B cell-specific immunoglobulin superfamily member, is a sialic acid-binding lectin. J Biol Chem. 1993;268(10):7011–8.

    CAS  PubMed  Google Scholar 

  132. Nitschke L, Carsetti R, Ocker B, Köhler G, Lamers MC. CD22 is a negative regulator of B-cell receptor signalling. Curr Biol. 1997;7(2):133–43.

    CAS  PubMed  Google Scholar 

  133. Nakashima H, Hamaguchi Y, Watanabe R, Ishiura N, Kuwano Y, Okochi H, et al. CD22 expression mediates the regulatory functions of peritoneal B-1a cells during the remission phase of contact hypersensitivity reactions. J Immunol. 2010;184(9):4637–45.

    PubMed Central  CAS  PubMed  Google Scholar 

  134. Sato S, Tuscano JM, Inaoki M, Tedder TF, editors. CD22 negatively and positively regulates signal transduction through the B lymphocyte antigen receptor. Semin Immunol. 1998;10(4):287–97.

    Google Scholar 

  135. Carnahan J, Wang P, Kendall R, Chen C, Hu S, Boone T, et al. Epratuzumab, a humanized monoclonal antibody targeting CD22 characterization of in vitro properties. Clin Cancer Res. 2003;9(10):3982s–90.

    CAS  PubMed  Google Scholar 

  136. Carnahan J, Stein R, Qu Z, Hess K, Cesano A, Hansen HJ, et al. Epratuzumab, a CD22-targeting recombinant humanized antibody with a different mode of action from rituximab. Mol Immunol. 2007;44(6):1331–41.

    CAS  PubMed  Google Scholar 

  137. Leonard JP, Coleman M, Ketas JC, Chadburn A, Ely S, Furman RR, et al. Phase I/II trial of epratuzumab (humanized anti-CD22 antibody) in indolent non-Hodgkin’s lymphoma. J Clin Oncol. 2003;21(16):3051–9.

    CAS  PubMed  Google Scholar 

  138. Leonard JP, Schuster SJ, Emmanouilides C, Couture F, Teoh N, Wegener WA, et al. Durable complete responses from therapy with combined epratuzumab and rituximab. Cancer. 2008;113(10):2714–23.

    CAS  PubMed  Google Scholar 

  139. Strauss SJ, Morschhauser F, Rech J, Repp R, Solal-Celigny P, Zinzani PL, et al. Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin’s lymphoma. J Clin Oncol. 2006;24(24):3880–6.

    CAS  PubMed  Google Scholar 

  140. Micallef IN, Kahl BS, Maurer MJ, Dogan A, Ansell SM, Colgan JP, et al. A pilot study of epratuzumab and rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated, diffuse large B‐cell lymphoma. Cancer. 2006;107(12):2826–32.

    CAS  PubMed  Google Scholar 

  141. Stein R, Qu Z, Chen S, Rosario A, Shi V, Hayes M, et al. Characterization of a new humanized anti-CD20 monoclonal antibody, IMMU-106, and its use in combination with the humanized anti-CD22 antibody, epratuzumab, for the therapy of non-Hodgkin’s lymphoma. Clin Cancer Res. 2004;10(8):2868–78.

    CAS  PubMed  Google Scholar 

  142. Rossi EA, Goldenberg DM, Cardillo TM, Stein R, Chang C-H. Hexavalent bispecific antibodies represent a new class of anticancer therapeutics: 1. Properties of anti-CD20/CD22 antibodies in lymphoma. Blood. 2009;113(24):6161–71.

    PubMed Central  CAS  PubMed  Google Scholar 

  143. Qu Z, Goldenberg DM, Cardillo TM, Shi V, Hansen HJ, Chang C-H. Bispecific anti-CD20/22 antibodies inhibit B-cell lymphoma proliferation by a unique mechanism of action. Blood. 2008;111(4):2211–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  144. DiJoseph JF, Popplewell A, Tickle S, Ladyman H, Lawson A, Kunz A, et al. Antibody-targeted chemotherapy of B-cell lymphoma using calicheamicin conjugated to murine or humanized antibody against CD22. Cancer Immunol Immunother. 2005;54(1):11–24.

    CAS  PubMed  Google Scholar 

  145. DiJoseph JF, Armellino DC, Boghaert ER, Khandke K, Dougher MM, Sridharan L, et al. Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignancies. Blood. 2004;103(5):1807–14.

    CAS  PubMed  Google Scholar 

  146. DiJoseph JF, Goad ME, Dougher MM, Boghaert ER, Kunz A, Hamann PR, et al. Potent and specific antitumor efficacy of CMC-544, a CD22-targeted immunoconjugate of calicheamicin, against systemically disseminated B-cell lymphoma. Clin Cancer Res. 2004;10(24):8620–9.

    CAS  PubMed  Google Scholar 

  147. DiJoseph JF, Dougher MM, Kalyandrug LB, Armellino DC, Boghaert ER, Hamann PR, et al. Antitumor efficacy of a combination of CMC-544 (inotuzumab ozogamicin), a CD22-targeted cytotoxic immunoconjugate of calicheamicin, and rituximab against non-Hodgkin’s B-cell lymphoma. Clin Cancer Res. 2006;12(1):242–9.

    CAS  PubMed  Google Scholar 

  148. Advani A, Coiffier B, Czuczman MS, Dreyling M, Foran J, Gine E, et al. Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin’s lymphoma: results of a phase I study. J Clin Oncol. 2010;28(12):2085–93.

    CAS  PubMed  Google Scholar 

  149. Dang NH, Smith MR, Offner F, Verhoef G, Johnson P, Rohatiner AZ et al., editors. Anti-CD22 immunoconjugate inotuzumab ozogamicin (CMC-544)+ rituximab: clinical activity including survival in patients with recurrent/refractory follicular or’aggressive’lymphoma. 51st Annual meeting of the American Society of Hematology. 2009;114:242–43.

    Google Scholar 

  150. van Kooten C, Banchereau J. CD40-CD40 ligand. J Leukoc Biol. 2000;67(1):2–17.

    PubMed  Google Scholar 

  151. Hock BD, McKenzie JL, Patton NW, Drayson M, Taylor K, Wakeman C, et al. Circulating levels and clinical significance of soluble CD40 in patients with hematologic malignancies. Cancer. 2006;106(10):2148–57.

    CAS  PubMed  Google Scholar 

  152. Younes A. The dynamics of life and death of malignant lymphocytes. Curr Opin Oncol. 1999;11(5):364.

    CAS  PubMed  Google Scholar 

  153. Oflazoglu E, Stone I, Brown L, Gordon K, van Rooijen N, Jonas M, et al. Macrophages and Fc-receptor interactions contribute to the antitumour activities of the anti-CD40 antibody SGN-40. Br J Cancer. 2008;100(1):113–7.

    PubMed Central  PubMed  Google Scholar 

  154. Kelley SK, Gelzleichter T, Xie D, Lee WP, Darbonne WC, Qureshi F, et al. Preclinical pharmacokinetics, pharmacodynamics, and activity of a humanized anti‐CD40 antibody (SGN‐40) in rodents and non‐human primates. Br J Pharmacol. 2006;148(8):1116–23.

    PubMed Central  CAS  PubMed  Google Scholar 

  155. Hussein M, Berenson JR, Niesvizky R, Munshi N, Matous J, Sobecks R, et al. A phase I multidose study of dacetuzumab (SGN-40; humanized anti-CD40 monoclonal antibody) in patients with multiple myeloma. Haematologica. 2010;95(5):845–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  156. Advani R, Forero-Torres A, Furman RR, Rosenblatt JD, Younes A, Ren H, et al. Phase I study of the humanized anti-CD40 monoclonal antibody dacetuzumab in refractory or recurrent non-Hodgkin’s lymphoma. J Clin Oncol. 2009;27(26):4371–7.

    CAS  PubMed  Google Scholar 

  157. Lugman M, Tong X, Niu X. CHIR-12.12, an antagonist anti-CD40 63. antibody, exhibits greater ADCC than rituximab against a variety of malignant B cells: evaluation of FcyRIIIa polymorphism and ADCC response [abstract no. 1472]. Blood. 2005;106:424a.

    Google Scholar 

  158. Tedder TF, Inaoki M, Sato S. The CD19–CD21 complex regulates signal transduction thresholds governing humoral immunity and autoimmunity. Immunity. 1997;6(2):107–18.

    CAS  PubMed  Google Scholar 

  159. Sato S, Steeber DA, Jansen PJ, Tedder TF. CD19 expression levels regulate B lymphocyte development: human CD19 restores normal function in mice lacking endogenous CD19. J Immunol. 1997;158(10):4662–9.

    CAS  PubMed  Google Scholar 

  160. Hooijberg E, van den Berk PC, Sein JJ, Wijdenes J, Hart AA, de Boer RW, et al. Enhanced antitumor effects of CD20 over CD19 monoclonal antibodies in a nude mouse xenograft model. Cancer Res. 1995;55(4):840–6.

    CAS  PubMed  Google Scholar 

  161. Horton HM, Bernett MJ, Pong E, Peipp M, Karki S, Chu SY, et al. Potent in vitro and in vivo activity of an Fc-engineered anti-CD19 monoclonal antibody against lymphoma and leukemia. Cancer Res. 2008;68(19):8049–57.

    CAS  PubMed  Google Scholar 

  162. Awan FT, Lapalombella R, Trotta R, Butchar JP, Yu B, Benson DM, et al. CD19 targeting of chronic lymphocytic leukemia with a novel Fc-domain–engineered monoclonal antibody. Blood. 2010;115(6):1204–13.

    PubMed Central  CAS  PubMed  Google Scholar 

  163. Reusch ULG, Hensel M, et al. Effect of tetravalent bispecific CD19xCD3 recombinant antibody construct and CD28 costimulation on lysis of malignant B cells from patients with chronic lymphocytic leukemia by autologous T cells. Int J Cancer. 2004;112:509–18.

    CAS  PubMed  Google Scholar 

  164. Manzke OTH, Borchmann P, et al. Locoregional treatment of low-grade B-cell lymphoma with CD3xCD19 bispecific antibodies and CD28 costimulation I. Clinical phase I evaluation. Int J Cancer. 2001;91(4):508–15.

    CAS  PubMed  Google Scholar 

  165. Bargou R, Leo E, Zugmaier G, Klinger M, Goebeler M, Knop S, et al. Tumor regression in cancer patients by very low doses of a T cell–engaging antibody. Science. 2008;321(5891):974–7.

    CAS  PubMed  Google Scholar 

  166. Löffler A, Kufer P, Lutterbüse R, Zettl F, Daniel PT, Schwenkenbecher JM, et al. A recombinant bispecific single-chain antibody, CD19× CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes. Blood. 2000;95(6):2098–103.

    PubMed  Google Scholar 

  167. Al-Katib AM, Aboukameel A, Mohammad R, Bissery M-C, Zuany-Amorim C. Superior antitumor activity of SAR3419 to rituximab in xenograft models for non-Hodgkin’s lymphoma. Clin Cancer Res. 2009;15(12):4038–45.

    CAS  PubMed  Google Scholar 

  168. Younes A, Kim S, Romaguera J. Copeland AR, de Castro Farial S, et al. Phase I multi-dose escalation study of the anti-CD19 maytansinoid immunoconjugate SAR3419 administered by intravenous(IV) infusion every 3 weeks to patients with relapsed/refractory B-cell non-Hodgkin’s lymphoma (NHL). J Clin Oncol. 2012;30(22):2776–82.

    Google Scholar 

  169. Classon BJ, Williams AF, Willis AC, Seed B, Stamenkovic I. The primary structure of the human leukocyte antigen CD37, a species homologue of the rat MRC OX-44 antigen. J Exp Med. 1989;169(4):1497–502.

    CAS  PubMed  Google Scholar 

  170. Schwartz-Albiez R, Dörken B, Hofmann W, Moldenhauer G. The B cell-associated CD37 antigen (gp40-52). Structure and subcellular expression of an extensively glycosylated glycoprotein. J Immunol. 1988;140(3):905–14.

    CAS  PubMed  Google Scholar 

  171. Smeland E, Funderud S, Ruud E, Blomhoff H, Godal T. Characterization of two murine monoclonal antibodies reactive with human B cells. Scand J Immunol. 1985;21(3):205–14.

    CAS  PubMed  Google Scholar 

  172. Nuckel H, Frey U, Roth A, et al. Alemtuzumab induces enhanced apoptosis in vitro in B-cells from patients with chronic lymphocytic leukemia by antibody-dependent cellular cytotoxicity. Eur J Pharmacol. 2005;514(2–3):217–24.

    PubMed  Google Scholar 

  173. Gallamini A, Zaja F, Patti C, et al. Alemtuzumab (Campath-1H) and CHOP chemotherapy as first-line treatment of peripheral T-cell lymphoma: results of a GITIL. Blood. 2007;7(110):2316–23.

    Google Scholar 

  174. Czajczynska AGA, Repp R, Humpe A, Schub N, Raff T, Nickelsen M, Schrauder A, Schrappe M, Kneba M, Gramatzki M. Allogeneic stem cell transplantation with BEAM and alemtuzumab conditioning immediately after remission induction has curative potential in advanced T-cell non-Hodgkin’s lymphoma. Biol Blood Marrow Transplant. 2013;19(11):1632–7.

    CAS  PubMed  Google Scholar 

  175. Dakappagari N, Ho SN, Gascoyne RD, Ranuio J, Weng AP, Tangri S. CD80 (B7. 1) is expressed on both malignant B cells and nonmalignant stromal cells in non‐Hodgkin lymphoma. Cytom B Clin Cytom. 2012;82(2):112–9.

    Google Scholar 

  176. Schultze J, Nadler L, Gribben J. B7-mediated costimulation and the immune response. Blood Rev. 1996;10(2):111–27.

    CAS  PubMed  Google Scholar 

  177. Younes A, Hariharan K, Allen RS, Leigh BR. Initial trials of anti-CD80 monoclonal antibody (Galiximab) therapy for patients with relapsed or refractory follicular lymphoma. Clin Lymphoma Myeloma Leuk. 2003;3(4):257–9.

    CAS  Google Scholar 

  178. Bhat S, Czuczman MS. Galiximab: a review. Expert Opin Biol Ther. 2010;10(3):451–8.

    CAS  PubMed  Google Scholar 

  179. Czuczman MS, Thall A, Witzig TE, Vose JM, Younes A, Emmanouilides C, et al. Phase I/II study of galiximab, an anti-CD80 antibody, for relapsed or refractory follicular lymphoma. J Clin Oncol. 2005;23(19):4390–8.

    CAS  PubMed  Google Scholar 

  180. Stein R, Mattes MJ, Cardillo TM, Hansen HJ, Chang C-H, Burton J, et al. CD74: a new candidate target for the immunotherapy of B-cell neoplasms. Clin Cancer Res. 2007;13(18):5556s–63.

    CAS  PubMed  Google Scholar 

  181. Starlets D, Gore Y, Binsky I, Haran M, Harpaz N, Shvidel L, et al. Cell-surface CD74 initiates a signaling cascade leading to cell proliferation and survival. Blood. 2006;107(12):4807–16.

    CAS  PubMed  Google Scholar 

  182. Leng L, Metz CN, Fang Y, Xu J, Donnelly S, Baugh J, et al. MIF signal transduction initiated by binding to CD74. J Exp Med. 2003;197(11):1467–76.

    PubMed Central  CAS  PubMed  Google Scholar 

  183. Sapra P, Stein R, Pickett J, Qu Z, Govindan SV, Cardillo TM, et al. Anti-CD74 antibody-doxorubicin conjugate, IMMU-110, in a human multiple myeloma xenograft and in monkeys. Clin Cancer Res. 2005;11(14):5257–64.

    CAS  PubMed  Google Scholar 

  184. Chang C-H, Sapra P, Vanama SS, Hansen HJ, Horak ID, Goldenberg DM. Effective therapy of human lymphoma xenografts with a novel recombinant ribonuclease/anti-CD74 humanized IgG4 antibody immunotoxin. Blood. 2005;106(13):4308–14.

    CAS  PubMed  Google Scholar 

  185. Gingrich RD, Dahle CE, Hoskins KF, Senneff M. Identification and characterization of a new surface membrane antigen found predominantly on malignant B lymphocytes. Blood. 1990;75(12):2375–87.

    CAS  PubMed  Google Scholar 

  186. Stockmeyer B, Schiller M, Repp R, Lorenz HM, Kalden JR, Gramatzki M, et al. Enhanced killing of B lymphoma cells by granulocyte colony‐stimulating factor‐primed effector cells and Hu1D10–a humanized human leucocyte antigen DR antibody. Br J Haematol. 2002;118(4):959–67.

    CAS  PubMed  Google Scholar 

  187. Shi JD, Bullock C, Hall WC, Wescott V, Wang H, Levitt DJ, et al. In vivo pharmacodynamic effects of Hu1D10 (remitogen), a humanized antibody reactive against a polymorphic determinant of HLA-DR expressed on B cells. Leuk Lymphoma. 2002;43(6):1303–12.

    CAS  PubMed  Google Scholar 

  188. Tay K, Dunleavy K, Wilson WH. Targeting HLA-DR. Leuk Lymphoma. 2009;50(12):1911–3.

    CAS  PubMed  Google Scholar 

  189. Dunleavy K, White T, Grant N, Shovlin M, Stetler-Stevenson M, Pittaluga S et al., editors. Phase 1 study of combination rituximab with apolizumab in relapsed/refractory B-cell lymphoma and chronic lymphocytic leukemia. J Clin Oncol (Meeting Abstracts). 2005;23(Suppl 16):1607.

    Google Scholar 

  190. Gupta P, Goldenberg DM, Rossi EA, Chang C-H. Multiple signaling pathways induced by hexavalent, monospecific, anti-CD20 and hexavalent, bispecific, anti-CD20/CD22 humanized antibodies correlate with enhanced toxicity to B-cell lymphomas and leukemias. Blood. 2010;116(17):3258–67.

    PubMed Central  CAS  PubMed  Google Scholar 

  191. Stein R, Qu Z, Chen S, Solis D, Hansen HJ, Goldenberg DM. Characterization of a humanized IgG4 anti-HLA-DR monoclonal antibody that lacks effector cell functions but retains direct antilymphoma activity and increases the potency of rituximab. Blood. 2006;108(8):2736–44.

    PubMed Central  CAS  PubMed  Google Scholar 

  192. Stein R, Gupta P, Chen X, Cardillo TM, Furman RR, Chen S, et al. Therapy of B-cell malignancies by anti–HLA-DR humanized monoclonal antibody, IMMU-114, is mediated through hyperactivation of ERK and JNK MAP kinase signaling pathways. Blood. 2010;115(25):5180–90.

    PubMed Central  CAS  PubMed  Google Scholar 

  193. Liu C, DeNardo G, Tobin E, DeNardo S. Antilymphoma effects of anti-HLA-DR and CD20 monoclonal antibodies (Lym-1 and Rituximab) on human lymphoma cells. Cancer Biother Radiopharm. 2004;19(5):545–61.

    CAS  PubMed  Google Scholar 

  194. Hu E, Epstein AL, Naeve GS, Gill I, Martin S, Sherrod A, et al. A phase 1a clinical trial of LYM‐1 monoclonal antibody serotherapy in patients with refractory b cell malignancies. Hematol Oncol. 1989;7(2):155–66.

    CAS  PubMed  Google Scholar 

  195. DeNardo GL, O’Donnell RT, Rose LM, Mirick GR, Kroger LA, DeNardo SJ. Milestones in the development of Lym-1 therapy. Hybridoma. 1999;18(1):1–11.

    CAS  PubMed  Google Scholar 

  196. O’Donnell RT, Shen S, Denardo SJ, Wun T, Kukis DL, Goldstein DS, et al. A phase I study of 90Y-2IT-BAD-Lym-1 in patients with non-Hodgkin’s lymphoma. Anticancer Res. 1999;20(5C):3647–55.

    Google Scholar 

  197. O’Donnell RT, DeNardo GL, Kukis DL, Lamborn KR, Shen S, Yuan A, et al. A clinical trial of radioimmunotherapy with 67Cu-21T.-BAT-Lym-1for non-Hodgkin’s lymphoma. J Nucl Med. 1999;40:2014–20.

    PubMed  Google Scholar 

  198. DeNardo GL, Tobin E, Chan K, Bradt BM, DeNardo SJ. Direct antilymphoma effects on human lymphoma cells of monotherapy and combination therapy with CD20 and HLA-DR antibodies and 90Y-labeled HLA-DR antibodies. Clin Cancer Res. 2005;11(19):7075s–9.

    CAS  PubMed  Google Scholar 

  199. DeNardo GL, Hok S, Natarajan A, Cosman M, DeNardo SJ, Lightstone FC, et al. Characteristics of dimeric (bis) bidentate selective high affinity ligands as HLA-DR10 beta antibody mimics targeting non-Hodgkin’s lymphoma. Int J Oncol. 2007;31(4):729–40.

    CAS  PubMed  Google Scholar 

  200. DeNardo GL, Natarajan A, Hok S, Perkins J, Cosman M, DeNardo SJ, et al. Pharmacokinetic characterization in xenografted mice of a series of first-generation mimics for HLA-DR antibody, Lym-1, as carrier molecules to image and treat lymphoma. J Nucl Med. 2007;48(8):1338–47.

    CAS  PubMed  Google Scholar 

  201. West J, Perkins J, Hok S, Balhorn R, Lightstone FC, Cosman M, et al. Direct antilymphoma activity of novel, first-generation “antibody mimics” that bind HLA-DR10-positive non-Hodgkin’s lymphoma cells. Cancer Biother Radiopharm. 2006;21(6):645–54.

    CAS  PubMed  Google Scholar 

  202. Renukaradhya GJ, Khan MA, Vieira M, Du W, Gervay-Hague J, Brutkiewicz RR. Type I NKT cells protect (and type II NKT cells suppress) the host’s innate antitumor immune response to a B-cell lymphoma. Blood. 2008;111(12):5637–45.

    PubMed Central  CAS  PubMed  Google Scholar 

  203. Xu C, de Vries R, Visser L, Diepstra A, Gadola SD, Poppema S, et al. Expression of CD1d and presence of invariant NKT cells in classical Hodgkin lymphoma. Am J Hematol. 2010;85(7):539–41.

    PubMed  Google Scholar 

  204. Song L, Ashgharzadeh S, Salo J, Engell K, Sposto R, Ara T, Silverman AM, DeClerck YA, Seeger RC, Metelitsa LS. Valpha24-invariant NKT cells mediate anti-tumor activity via killing of tumor-associated macrophages. J Clin Invest. 2009;119:1524–36.

    PubMed Central  CAS  PubMed  Google Scholar 

  205. Steidl C, Lee T, Shah SP, Farinha P, Han G, Nayar T, et al. Tumor-associated macrophages and survival in classic Hodgkin’s lymphoma. N Engl J Med. 2010;362(10):875–85.

    PubMed Central  CAS  PubMed  Google Scholar 

  206. Metelitsa LS. Anti-tumor potential of type-I NKT cells against CD1d-positive and CD1d-negative tumors in humans. Clin Immunol. 2011;140(2):119–29.

    PubMed Central  CAS  PubMed  Google Scholar 

  207. Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, et al. Innate or adaptive immunity? The example of natural killer cells. Science. 2011;331(6013):44–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  208. Sulica A, Morel R, Metes D, Herberman R. Ig-binding receptors on human NK cells as effector and regulatory surface molecules. Int Rev Immunol. 2001;20(3–4):371–414.

    CAS  PubMed  Google Scholar 

  209. Terunuma H, Deng X, Dewan Z, Fujimoto S, Yamamoto N. Potential role of NK cells in the induction of immune responses: implications for NK cell-based immunotherapy for cancers and viral infections. Int Rev Immunol. 2008;27(3):93–110.

    CAS  PubMed  Google Scholar 

  210. Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K. Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet. 2000;356(9244):1795–9.

    CAS  PubMed  Google Scholar 

  211. Miller JS, Soignier Y, Panoskaltsis-Mortari A, McNearney SA, Yun GH, Fautsch SK, et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood. 2005;105(8):3051–7.

    CAS  PubMed  Google Scholar 

  212. Yang Q, Hokland ME, Bryant JL, Zhang Y, Nannmark U, Watkins SC, et al. Tumor‐localization by adoptively transferred, interleukin‐2‐activated NK cells leads to destruction of well‐established lung metastases. Int J Cancer. 2003;105(4):512–9.

    CAS  PubMed  Google Scholar 

  213. Pegram HJ, Jackson JT, Smyth MJ, Kershaw MH, Darcy PK. Adoptive transfer of gene-modified primary NK cells can specifically inhibit tumor progression in vivo. J Immunol. 2008;181(5):3449–55.

    CAS  PubMed  Google Scholar 

  214. Terme M, Ullrich E, Delahaye NF, Chaput N, Zitvogel L. Natural killer cell–directed therapies: moving from unexpected results to successful strategies. Nat Immunol. 2008;9(5):486–94.

    CAS  PubMed  Google Scholar 

  215. Deng X, Terunuma H, Nieda M, Xiao W, Nicol A. Synergistic cytotoxicity of ex vivo expanded natural killer cells in combination with monoclonal antibody drugs against cancer cells. Int Immunopharmacol. 2012;14(4):593–605.

    CAS  PubMed  Google Scholar 

  216. Fujisaki H, Kakuda H, Shimasaki N, Imai C, Ma J, Lockey T, et al. Expansion of highly cytotoxic human natural killer cells for cancer cell therapy. Cancer Res. 2009;69(9):4010–7.

    PubMed Central  CAS  PubMed  Google Scholar 

  217. Harada H, Saijo K, Watanabe S, Tsuboi K, Nose T, Ishiwata I, et al. Selective expansion of human natural killer cells from peripheral blood mononuclear cells by the cell line, HFWT. Cancer Sci. 2002;93(3):313–9.

    CAS  Google Scholar 

  218. Sutlu T, Stellan B, Gilljam M, Quezada HC, Nahi H, Gahrton G, et al. Clinical-grade, large-scale, feeder-free expansion of highly active human natural killer cells for adoptive immunotherapy using an automated bioreactor. Cytotherapy. 2010;12(8):1044–55.

    CAS  PubMed  Google Scholar 

  219. Luhm J, Brand J-M, Koritke P, Höppner M, Kirchner H, Frohn C. Large-scale generation of natural killer lymphocytes for clinical application. J Hematother Stem Cell Res. 2002;11(4):651–7.

    PubMed  Google Scholar 

  220. Berg M, Lundqvist A, McCoy Jr P, Samsel L, Fan Y, Tawab A, et al. Clinical-grade ex vivo-expanded human natural killer cells up-regulate activating receptors and death receptor ligands and have enhanced cytolytic activity against tumor cells. Cytotherapy. 2009;11(3):341–55.

    Google Scholar 

  221. Pievani A, Belussi C, Klein C, Rambaldi A, Golay J, Introna M. Enhanced killing of human B-cell lymphoma targets by combined use of cytokine-induced killer cell (CIK) cultures and anti-CD20 antibodies. Blood. 2011;117(2):510–8.

    CAS  PubMed  Google Scholar 

  222. Gennari R, Menard S, Fagnoni F, Ponchio L, Scelsi M, Tagliabue E, et al. Pilot study of the mechanism of action of preoperative trastuzumab in patients with primary operable breast tumors overexpressing HER2. Clin Cancer Res. 2004;10(17):5650–5.

    CAS  PubMed  Google Scholar 

  223. Beano A, Signorino E, Evangelista A, Brusa D, Mistrangelo M, Polimeni MA, et al. Correlation between NK function and response to trastuzumab in metastatic breast cancer patients. J Transl Med. 2008;6(1):25.

    PubMed Central  PubMed  Google Scholar 

  224. Kute TE, Savage L, Stehle Jr JR, Kim-Shapiro JW, Blanks MJ, Wood J, et al. Breast tumor cells isolated from in vitro resistance to trastuzumab remain sensitive to trastuzumab anti-tumor effects in vivo and to ADCC killing. Cancer Immunol Immunother. 2009;58(11):1887–96.

    CAS  PubMed  Google Scholar 

  225. Maréchal R, De Schutter J, Nagy N, Demetter P, Lemmers A, Devière J, et al. Putative contribution of CD56 positive cells in cetuximab treatment efficacy in first-line metastatic colorectal cancer patients. BMC Cancer. 2010;10(1):340.

    PubMed Central  PubMed  Google Scholar 

  226. Siders WM, Shields J, Garron C, Hu Y, Boutin P, Shankara S, et al. Involvement of neutrophils and natural killer cells in the anti-tumor activity of alemtuzumab in xenograft tumor models. Leuk Lymphoma. 2010;51(7):1293–304.

    CAS  PubMed  Google Scholar 

  227. Baron S, Tyring SK, Fleischmann Jr WR, Coppenhaver DH, Niesel DW, Klimpel GR, et al. The interferons. JAMA. 1991;266(10):1375–83.

    CAS  PubMed  Google Scholar 

  228. McLaughlin P. The role of interferon in the therapy of low grade lymphoma. Leuk Lymphoma. 1993;10(S1):17–20.

    PubMed  Google Scholar 

  229. Janssen JTP, Ludwig H, Scheithauer W, De Pauw B, Keyser A, Van Tol R, et al. Phase I study of recombinant human interferon alpha-2C in patients with chemotherapy-refractory malignancies. Oncology. 1985;42 Suppl 1:3–6.

    PubMed  Google Scholar 

  230. Leavitt R, Ratanatharathorn V, Ozer H, Ultmann J, Portlock C, Myers J et al., editors. Alfa-2b interferon in the treatment of Hodgkin’s disease and non-Hodgkin’s lymphoma. Semin Oncol. 1987;14(2 Suppl 2):18.

    Google Scholar 

  231. Davis TA, Maloney DG, Grillo-López AJ, White CA, Williams ME, Weiner GJ, et al. Combination immunotherapy of relapsed or refractory low-grade or follicular non-Hodgkin’s lymphoma with rituximab and interferon-α-2a. Clin Cancer Res. 2000;6(7):2644–52.

    CAS  PubMed  Google Scholar 

  232. Salles G, Mounier N, de Guibert S, Morschhauser F, Doyen C, Rossi J-F, et al. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood. 2008;112(13):4824–31.

    CAS  PubMed  Google Scholar 

  233. Rohatiner A, Gregory W, Peterson B, Borden E, Solal-Celigny P, Hagenbeek A, et al. Meta-analysis to evaluate the role of interferon in follicular lymphoma. J Clin Oncol. 2005;23(10):2215–23.

    CAS  PubMed  Google Scholar 

  234. Kreitman RJ, Pastan I. Recombinant single-chain immunotoxins against T and B cell leukemias. Leuk Lymphoma. 1994;13(1–2):1.

    CAS  PubMed  Google Scholar 

  235. Yamauchi T, Matsuda Y, Takai M, Tasaki T, Tai K, Hosono N, et al. Early relapse is associated with high serum soluble onterleukin-2 receptor after the sixth cycle of R-CHOP chemotherapy in patients with advanced diffuse large B-cell lymphoma. Anticancer Res. 2012;32(11):5051–7.

    CAS  PubMed  Google Scholar 

  236. Kitagawa J-i, Hara T, Tsurumi H, Goto N, Kanemura N, Yoshikawa T, et al. Serum-soluble interleukin-2 receptor (sIL-2R) is an extremely strong prognostic factor for patients with peripheral T-cell lymphoma, unspecified (PTCL-U). J Cancer Res Clin Oncol. 2009;135(1):53–9.

    CAS  PubMed  Google Scholar 

  237. Yoshizato T, Nannya Y, Imai Y, Ichikawa M, Kurokawa M. Clinical significance of serum-soluble interleukin-2 receptor in patients with follicular lymphoma. Clin Lymphoma Myeloma Leuk. 2013;13(4):410–6.

    CAS  PubMed  Google Scholar 

  238. Grille S, Brugnini A, Nese M, Corley E, Falkenberg FW, Lens D, et al. A B-cell lymphoma vaccine using a depot formulation of interleukin-2 induces potent antitumor immunity despite increased numbers of intratumoral regulatory T cells. Cancer Immunol Immunother. 2010;59(4):519–27.

    CAS  PubMed  Google Scholar 

  239. Slivnick DJ, Ellis TM, Nawrocki JF, Fisher RI. The impact of Hodgkin’s disease on the immune system. Semin Oncol. 1990;17(6):673–82.

    CAS  PubMed  Google Scholar 

  240. Ashkenazi A, Dixit VM. Apoptosis control by death and decoy receptors. Curr Opin Cell Biol. 1999;11(2):255–60.

    CAS  PubMed  Google Scholar 

  241. Pukac L, Kanakaraj P, Humphreys R, Alderson R, Bloom M, Sung C, et al. HGS-ETR1, a fully human TRAIL-receptor 1 monoclonal antibody, induces cell death in multiple tumour types in vitro and in vivo. Br J Cancer. 2005;92(8):1430–41.

    PubMed Central  CAS  PubMed  Google Scholar 

  242. Luster TA, Carrell JA, McCormick K, Sun D, Humphreys R. Mapatumumab and lexatumumab induce apoptosis in TRAIL-R1 and TRAIL-R2 antibody-resistant NSCLC cell lines when treated in combination with bortezomib. Mol Cancer Ther. 2009;8(2):292–302.

    CAS  PubMed  Google Scholar 

  243. Georgakis GV, Li Y, Humphreys R, Andreeff M, O’Brien S, Younes M, et al. Activity of selective fully human agonistic antibodies to the TRAIL death receptors TRAIL‐R1 and TRAIL‐R2 in primary and cultured lymphoma cells: induction of apoptosis and enhancement of doxorubicin‐and bortezomib‐induced cell death. Br J Haematol. 2005;130(4):501–10.

    CAS  PubMed  Google Scholar 

  244. Maddipatla S, Hernandez-Ilizaliturri FJ, Knight J, Czuczman MS. Augmented antitumor activity against B-cell lymphoma by a combination of monoclonal antibodies targeting TRAIL-R1 and CD20. Clin Cancer Res. 2007;13(15):4556–64.

    CAS  PubMed  Google Scholar 

  245. Tolcher AW, Mita M, Meropol NJ, von Mehren M, Patnaik A, Padavic K, et al. Phase I pharmacokinetic and biologic correlative study of mapatumumab, a fully human monoclonal antibody with agonist activity to tumor necrosis factor–related apoptosis-inducing ligand receptor-1. J Clin Oncol. 2007;25(11):1390–6.

    CAS  PubMed  Google Scholar 

  246. Wakelee H, Patnaik A, Sikic B, Mita M, Fox N, Miceli R, et al. Phase I and pharmacokinetic study of lexatumumab (HGS-ETR2) given every 2 weeks in patients with advanced solid tumors. Ann Oncol. 2010;21(2):376–81.

    PubMed Central  CAS  PubMed  Google Scholar 

  247. Kaplan-Lefko PJ, Graves JD, Zoog SJ, Pan Y, Wall J, Branstetter DG, et al. Conatumumab, a fully human agonist antibody to death receptor 5, induces apoptosis via caspase activation in multiple tumor types. Cancer Biol Ther. 2010;9(8):618–31.

    CAS  PubMed  Google Scholar 

  248. Yee L, Fanale M, Dimick K, Calvert S, Robins C, Ing J, et al. A phase IB safety and pharmacokinetic (PK) study of recombinant human Apo2L/TRAIL in combination with rituximab in patients with low-grade non-Hodgkin lymphoma. J Clin Oncol. 2007;25(18 Suppl):8078.

    Google Scholar 

  249. Daniel D, Yang B, Lawrence DA, Totpal K, Balter I, Lee WP, et al. Cooperation of the proapoptotic receptor agonist rhApo2L/TRAIL with the CD20 antibody rituximab against non-Hodgkin lymphoma xenografts. Blood. 2007;110(12):4037–46.

    CAS  PubMed  Google Scholar 

  250. Lundqvist A, Berg M, Smith A, Childs RW. Bortezomib treatment to potentiate the anti-tumor immunity of ex-vivo expanded adoptively infused autologous natural killer cells. J Cancer. 2011;2:383.

    PubMed Central  CAS  PubMed  Google Scholar 

  251. Schiffer S, Hansen H, Hehmann-Titt G, Huhn M, Fischer R, Barth S, et al. Efficacy of an adapted granzyme B-based anti-CD30 cytolytic fusion protein against PI-9-positive classical Hodgkin lymphoma cells in a murine model. Blood Cancer J. 2013;3(3):e106.

    PubMed Central  CAS  PubMed  Google Scholar 

  252. Maunch PM, Armitage JO, Diehl V, Hoppe RT, Weiss LM, editors. Hodgkin’s disease. Philadelphia: Lippincott Williams & Wilkins; 1999.

    Google Scholar 

  253. DeMonaco NA, Wu M, Osborn J, Evans T, Foon KA, Swerdlow SH, et al. Phase II trial of abbreviated CHOP-rituximab followed by 90Y ibritumomab tiuxetan (Zevalin) and rituximab in patients with previously-untreated follicular non-Hodgkin lymphoma (NHL). Blood. 2005;106(11):2449.

    Google Scholar 

  254. Kaminski MS, Tuck M, Estes J, Kolstad A, Ross CW, Zasadny K, et al. 131I-tositumomab therapy as initial treatment for follicular lymphoma. N Engl J Med. 2005;352(5):441–9.

    CAS  PubMed  Google Scholar 

  255. Morschhauser F, Radford J, Van Hoof A, Vitolo U, Soubeyran P, Tilly H, et al. Phase III trial of consolidation therapy with yttrium-90–ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. J Clin Oncol. 2008;26(32):5156–64.

    CAS  PubMed  Google Scholar 

  256. DeNardo GL, DeNardo SJ, Goldstein DS, Kroger LA, Lamborn KR, Levy NB, et al. Maximum-tolerated dose, toxicity, and efficacy of (131) I-Lym-1 antibody for fractionated radioimmunotherapy of non-Hodgkin’s lymphoma. J Clin Oncol. 1998;16(10):3246–56.

    CAS  PubMed  Google Scholar 

  257. Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmanouilides C, Joyce R, et al. Randomized controlled trial of yttrium-90–labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma. J Clin Oncol. 2002;20(10):2453–63.

    CAS  PubMed  Google Scholar 

  258. Horning SJ, Younes A, Jain V, Kroll S, Lucas J, Podoloff D, et al. Efficacy and safety of tositumomab and iodine-131 tositumomab (Bexxar) in B-cell lymphoma, progressive after rituximab. J Clin Oncol. 2005;23(4):712–9.

    CAS  PubMed  Google Scholar 

  259. Witzig TE, Flinn IW, Gordon LI, Emmanouilides C, Czuczman MS, Saleh MN, et al. Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin’s lymphoma. J Clin Oncol. 2002;20(15):3262–9.

    CAS  PubMed  Google Scholar 

  260. Vose JM, Wahl RL, Saleh M, Rohatiner AZ, Knox SJ, Radford JA, et al. Multicenter phase II study of iodine-131 tositumomab for chemotherapy-relapsed/refractory low-grade and transformed low-grade B-cell non-Hodgkin’s lymphomas. J Clin Oncol. 2000;18(6):1316–23.

    CAS  PubMed  Google Scholar 

  261. Reff ME, Carner K, Chambers K, Chinn P, Leonard J, Raab R, et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood. 1994;83(2):435–45.

    CAS  PubMed  Google Scholar 

  262. Gopal AK, Press OW, Wilbur SM, Maloney DG, Pagel JM. Rituximab blocks binding of radiolabeled anti-CD20 antibodies (Ab) but not radiolabeled anti-CD45 Ab. Blood. 2008;112(3):830–5.

    PubMed Central  CAS  PubMed  Google Scholar 

  263. Wada N, Kohara M, Ogawa H, Sugiyama H, Fukuhara S, Tatsumi Y, et al. Change of CD20 expression in diffuse large B-cell lymphoma treated with rituximab, an anti-CD20 monoclonal antibody: a study of the Osaka Lymphoma Study Group. Case Rep Oncol. 2009;2(3):194–202.

    PubMed Central  CAS  PubMed  Google Scholar 

  264. Sugimoto T, Tomita A, Hiraga J, Shimada K, Kiyoi H, Kinoshita T, et al. Escape mechanisms from antibody therapy to lymphoma cells: downregulation of< i >CD20</i >mRNA by recruitment of the HDAC complex and not by DNA methylation. Biochem Biophys Res Commun. 2009;390(1):48–53.

    CAS  PubMed  Google Scholar 

  265. Gopal AK, Rajendran JG, Gooley TA, Pagel JM, Fisher DR, Petersdorf SH, et al. High-dose [131I] tositumomab (anti-CD20) radioimmunotherapy and autologous hematopoietic stem-cell transplantation for adults ≥ 60 years old with relapsed or refractory B-cell lymphoma. J Clin Oncol. 2007;25(11):1396–402.

    PubMed  Google Scholar 

  266. Press OW, Unger JM, Braziel RM, Maloney DG, Miller TP, LeBlanc M, et al. Phase II trial of CHOP chemotherapy followed by tositumomab/iodine I-131 tositumomab for previously untreated follicular non-Hodgkin’s lymphoma: five-year follow-up of Southwest Oncology Group Protocol S9911. J Clin Oncol. 2006;24(25):4143–9.

    CAS  PubMed  Google Scholar 

  267. Gordon LI, Witzig TE, Wiseman GA, Flinn IW, Spies SS, Silverman DH et al., editors. Yttrium 90 ibritumomab tiuxetan radioimmunotherapy for relapsed or refractory low-grade non-Hodgkin’s lymphoma. Semin Oncol. 2002;29(1):87–92.

    Google Scholar 

  268. Witzig TE, Molina A, Gordon LI, Emmanouilides C, Schilder RJ, Flinn IW, et al. Long‐term responses in patients with recurring or refractory B‐cell non‐Hodgkin lymphoma treated with yttrium 90 ibritumomab tiuxetan. Cancer. 2007;109(9):1804–10.

    CAS  PubMed  Google Scholar 

  269. Press OW, Eary JF, Appelbaum FR, Martin PJ, Badger CC, Nelp WB, et al. Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support. N Engl J Med. 1993;329(17):1219–24.

    CAS  PubMed  Google Scholar 

  270. Kaminski MS, Fig LM, Zasadny KR, Koral KF, DelRosario RB, Francis IR, et al. Imaging, dosimetry, and radioimmunotherapy with iodine 131-labeled anti-CD37 antibody in B-cell lymphoma. J Clin Oncol. 1992;10(11):1696–711.

    CAS  PubMed  Google Scholar 

  271. Eary JF, Press OW, Badger CC, Durack LD, Richter KY, Addison SJ, et al. Imaging and treatment of B-cell lymphoma. J Nucl Med Off Publ Soc Nucl Med. 1990;31(8):1257.

    CAS  Google Scholar 

  272. Sharkey RM, Behr TM, Mattes MJ, Stein R, Griffiths GL, Shih LB, et al. Advantage of residualizing radiolabels for an internalizing antibody against the B-cell lymphoma antigen, CD22. Cancer Immunol Immunother. 1997;44(3):179–88.

    CAS  PubMed  Google Scholar 

  273. Lub‐de Hooge MN, Kosterink JG, Perik PJ, Nijnuis H, Tran L, Bart J, et al. Preclinical characterisation of 111In‐DTPA‐trastuzumab. Br J Pharmacol. 2004;143(1):99–106.

    PubMed Central  PubMed  Google Scholar 

  274. Goldenberg DM, Horowitz J, Sharkey R, Hall T, Murthy S, Goldenberg H, et al. Targeting, dosimetry, and radioimmunotherapy of B-cell lymphomas with iodine-131-labeled LL2 monoclonal antibody. J Clin Oncol. 1991;9(4):548–64.

    CAS  PubMed  Google Scholar 

  275. Ghetie MA, Richardson J, Tucker T, Jones D, Uhr JW, Vitetta ES. Disseminated or localized growth of a human B‐cell tumor (Daudi) in scid mice. Int J Cancer. 1990;45(3):481–5.

    CAS  PubMed  Google Scholar 

  276. Repetto-Llamazares AH, Larsen RH, Mollatt C, Lassmann M, Dahle J. Biodistribution and dosimetry of 177Lu-tetulomab, a new radioimmunoconjugate for treatment of non-Hodgkin lymphoma. Curr Radiopharm. 2013;6(1):20.

    PubMed Central  CAS  PubMed  Google Scholar 

  277. Wang H, Wei H, Zhang R, Hou S, Li B, Qian W, et al. Genetically targeted T cells eradicate established breast cancer in syngeneic mice. Clin Cancer Res. 2009;15(3):943–50.

    CAS  PubMed  Google Scholar 

  278. Teng MW, Kershaw MH, Moeller M, Smyth MJ, Darcy PK. Immunotherapy of cancer using systemically delivered gene-modified human T lymphocytes. Hum Gene Ther. 2004;15(7):699–708.

    CAS  PubMed  Google Scholar 

  279. Haynes NM, Trapani JA, Teng MW, Jackson JT, Cerruti L, Jane SM, et al. Single-chain antigen recognition receptors that costimulate potent rejection of established experimental tumors. Blood. 2002;100(9):3155–63.

    CAS  PubMed  Google Scholar 

  280. Hombach A, Wieczarkowiecz A, Marquardt T, et al. Tumor-specific T cell activation by recombinant immunoreceptors: CD3 zeta signaling and CD28 costimulation are simultaneously required for efficient IL-2 secretion and can be integrated into one combined CD28/CD3 zeta signaling receptor molecule. J Immunol. 2001;167:6123–31.

    CAS  PubMed  Google Scholar 

  281. Rossig C, Brenner MK. Genetic modification of T lymphocytes for adoptive immunotherapy. Mol Ther. 2004;10(1):5–18.

    CAS  PubMed  Google Scholar 

  282. Jiang L, Yu K, Du J, Ni W, Han Y, Gao S, et al. Inhibition of p38 MAPK activity in B-NHL Raji cells by treatment with engineered CD20-specific T cells. Oncol Lett. 2011;2(4):753–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  283. Jensen M, Cooper L, Wu A, Forman S, Raubitschek A. Engineered CD20-specific primary human cytotoxic T lymphocytes for targeting B-cell malignancy. Cytotherapy. 2003;5(2):131–8.

    CAS  PubMed  Google Scholar 

  284. Eshhar Z, Waks T, Gross G, Schindler DG. Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proc Natl Acad Sci. 1993;90(2):720–4.

    PubMed Central  CAS  PubMed  Google Scholar 

  285. Yu K, Hu Y, Tan Y, et al. Immunotherapy of lymphomas with T cells modified by anti-CD20 scFv/CD28/CD3zeta recombinant gene. Leuk Lymphoma. 2008;49:1368–73.

    CAS  PubMed  Google Scholar 

  286. Parkhurst MR, Yang JC, Langan RC, Dudley ME, Nathan D-AN, Feldman SA, et al. T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol Ther. 2010;19(3):620–6.

    PubMed Central  PubMed  Google Scholar 

  287. Bendle GM, Linnemann C, Hooijkaas AI, Bies L, de Witte MA, Jorritsma A, et al. Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy. Nat Med. 2010;16(5):565–70.

    CAS  PubMed  Google Scholar 

  288. Rosenberg SA. Of mice, not men: no evidence for graft-versus-host disease in humans receiving T-cell receptor–transduced autologous T cells. Mol Ther. 2010;18(10):1744.

    PubMed Central  CAS  PubMed  Google Scholar 

  289. Pulè MA, Straathof KC, Dotti G, Heslop HE, Rooney CM, Brenner MK. A chimeric T cell antigen receptor that augments cytokine release and supports clonal expansion of primary human T cells. Mol Ther. 2005;12(5):933–41.

    PubMed  Google Scholar 

  290. Ngo MC, Rooney CM, Howard JM, Heslop HE. Ex vivo gene transfer for improved adoptive immunotherapy of cancer. Hum Mol Genet. 2011;20(R1):R93–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  291. Westwood JA, Kershaw MH. Genetic redirection of T cells for cancer therapy. J Leukoc Biol. 2010;87(5):791–803.

    CAS  PubMed  Google Scholar 

  292. Di Stasi A, De Angelis B, Rooney CM, Zhang L, Mahendravada A, Foster AE, et al. T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model. Blood. 2009;113(25):6392–402.

    PubMed Central  PubMed  Google Scholar 

  293. De Angelis B, Dotti G, Quintarelli C, Huye LE, Zhang L, Zhang M, et al. Generation of Epstein-Barr virus–specific cytotoxic T lymphocytes resistant to the immunosuppressive drug tacrolimus (FK506). Blood. 2009;114(23):4784–91.

    PubMed Central  PubMed  Google Scholar 

  294. Johnson LA, Morgan RA, Dudley ME, Cassard L, Yang JC, Hughes MS, et al. Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood. 2009;114(3):535–46.

    PubMed Central  CAS  PubMed  Google Scholar 

  295. Moritz D, Groner B. A spacer region between the single chain antibody-and the CD3 zeta-chain domain of chimeric T cell receptor components is required for efficient ligand binding and signaling activity. Gene Ther. 1995;2(8):539–46.

    CAS  PubMed  Google Scholar 

  296. Sadelain M, Brentjens R, Rivière I. The promise and potential pitfalls of chimeric antigen receptors. Curr Opin Immunol. 2009;21(2):215–23.

    CAS  PubMed  Google Scholar 

  297. Beckman RA, Weiner LM, Davis HM. Antibody constructs in cancer therapy. Cancer. 2007;109(2):170–9.

    CAS  PubMed  Google Scholar 

  298. Weijtens ME, Willemsen RA, Valerio D, Stam K, Bolhuis R. Single chain Ig/gamma gene-redirected human T lymphocytes produce cytokines, specifically lyse tumor cells, and recycle lytic capacity. J Immunol. 1996;157(2):836–43.

    CAS  PubMed  Google Scholar 

  299. Pule MA, Savoldo B, Myers GD, Rossig C, Russell HV, Dotti G, et al. Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nat Med. 2008;14(11):1264–70.

    PubMed Central  CAS  PubMed  Google Scholar 

  300. Geiger TL, Nguyen P, Leitenberg D, Flavell RA. Integrated src kinase and costimulatory activity enhances signal transduction through single-chain chimeric receptors in T lymphocytes. Blood. 2001;98(8):2364–71.

    CAS  PubMed  Google Scholar 

  301. Brentjens RJ, Santos E, Nikhamin Y, Yeh R, Matsushita M, La Perle K, et al. Genetically targeted T cells eradicate systemic acute lymphoblastic leukemia xenografts. Clin Cancer Res. 2007;13(18):5426–35.

    CAS  PubMed  Google Scholar 

  302. Kochenderfer JN, Wilson WH, Janik JE, Dudley ME, Stetler-Stevenson M, Feldman SA, et al. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood. 2010;116(20):4099–102.

    PubMed Central  CAS  PubMed  Google Scholar 

  303. Jena B, Dotti G, Cooper LJ. Redirecting T-cell specificity by introducing a tumor-specific chimeric antigen receptor. Blood. 2010;116(7):1035–44.

    PubMed Central  CAS  PubMed  Google Scholar 

  304. Ahmed N, Salsman VS, Yvon E, Louis CU, Perlaky L, Wels WS, et al. Immunotherapy for osteosarcoma: genetic modification of T cells overcomes low levels of tumor antigen expression. Mol Ther. 2009;17(10):1779–87.

    PubMed Central  CAS  PubMed  Google Scholar 

  305. Heslop HE. Safer cars. Mol Ther. 2010;18(4):661.

    PubMed Central  CAS  PubMed  Google Scholar 

  306. Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther. 2010;18(4):843–51.

    PubMed Central  CAS  PubMed  Google Scholar 

  307. Smyth MJ, Cretney E, Kelly JM, Westwood JA, Street SE, Yagita H, et al. Activation of NK cell cytotoxicity. Mol Immunol. 2005;42(4):501–10.

    CAS  PubMed  Google Scholar 

  308. Müller T, Uherek C, Maki G, Chow KU, Schimpf A, Klingemann H-G, et al. Expression of a CD20-specific chimeric antigen receptor enhances cytotoxic activity of NK cells and overcomes NK-resistance of lymphoma and leukemia cells. Cancer Immunol Immunother. 2008;57(3):411–23.

    PubMed  Google Scholar 

  309. Altvater B, Landmeier S, Pscherer S, Temme J, Schweer K, Kailayangiri S, et al. 2B4 (CD244) signaling by recombinant antigen-specific chimeric receptors costimulates natural killer cell activation to leukemia and neuroblastoma cells. Clin Cancer Res. 2009;15(15):4857–66.

    PubMed Central  CAS  PubMed  Google Scholar 

  310. Jiang W, Zhang J, Tian Z. Functional characterization of interleukin-15 gene transduction into the human natural killer cell line NKL. Cytotherapy. 2008;10(3):265–74.

    CAS  PubMed  Google Scholar 

  311. Pizzoferrato E. B7‐2 expression above a threshold elicits anti‐tumor immunity as effective as interleukin‐12 and prolongs survival in murine B‐cell lymphoma. Int J Cancer. 2004;110(1):61–9.

    CAS  PubMed  Google Scholar 

  312. Moreno M, Kramer MG, Yim L, Chabalgoity JA. Salmonella as live trojan horse for vaccine development and cancer gene therapy. Current Gene Ther. 2010;10(1):56–76.

    CAS  Google Scholar 

  313. Toso JF, Gill VJ, Hwu P, Marincola FM, Restifo NP, Schwartzentruber DJ, et al. Phase I study of the intravenous administration of attenuated Salmonella typhimurium to patients with metastatic melanoma. J Clin Oncol. 2002;20(1):142–52.

    PubMed Central  PubMed  Google Scholar 

  314. Heimann DM, Rosenberg SA. Continuous intravenous administration of live genetically modified salmonella typhimurium in patients with metastatic melanoma. J Immunother. 2003;26(2):179.

    PubMed Central  PubMed  Google Scholar 

  315. Spaner D, Shi Y, White D, Shaha S, He L, Masellis A, et al. A phase I/II trial of TLR-7 agonist immunotherapy in chronic lymphocytic leukemia. Leukemia. 2009;24(1):222–6.

    PubMed  Google Scholar 

  316. Spaner D, Masellis A. Toll-like receptor agonists in the treatment of chronic lymphocytic leukemia. Leukemia. 2006;21(1):53–60.

    PubMed  Google Scholar 

  317. Månsson A, Adner M, Höckerfelt U, Cardell LO. A distinct Toll‐like receptor repertoire in human tonsillar B cells, directly activated by Pam3CSK4, R‐837 and CpG‐2006 stimulation. Immunology. 2006;118(4):539–48.

    PubMed Central  PubMed  Google Scholar 

  318. Kumar H, Kawai T, Akira S. Toll-like receptors and innate immunity. Biochem Biophys Res Commun. 2009;388(4):621–5.

    CAS  PubMed  Google Scholar 

  319. Delbridge LM, O’Riordan MX. Innate recognition of intracellular bacteria. Curr Opin Immunol. 2007;19(1):10–6.

    CAS  PubMed  Google Scholar 

  320. Andersen MH, Schrama D, Thor Straten P, Becker JC. Cytotoxic T cells. J Invest Dermatol. 2006;126(1):32–41.

    CAS  PubMed  Google Scholar 

  321. Houghton AM. The paradox of tumor-associated neutrophils: fueling tumor growth with cytotoxic substances. Cell Cycle. 2010;9(9):1732–7.

    CAS  PubMed  Google Scholar 

  322. Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L, et al. Polarization of tumor-associated neutrophil phenotype by TGF-β:“N1” versus “N2” TAN. Cancer Cell. 2009;16(3):183–94.

    PubMed Central  CAS  PubMed  Google Scholar 

  323. Pohl C, Renner C, Schwonzen M, Schobert I, Liebenberg V, Wolf J, et al. CD30‐specific AB1‐AB2‐AB3 internal image antibody network: Potential use as anti‐idiotype vaccine against Hodgkin’s lymphoma. Int J Cancer. 1993;54(3):418–25.

    CAS  PubMed  Google Scholar 

  324. Iurescia S, Fioretti D, Fazio VM, Rinaldi M. Epitope-driven DNA vaccine design employing immunoinformatics against B-cell lymphoma: a biotech’s challenge. Biotechnol Adv. 2012;30(1):372–83.

    CAS  PubMed  Google Scholar 

  325. Fioretti D, Iurescia S, Fazio VM, Rinaldi M. DNA vaccines: developing new strategies against cancer. BioMed Res Int. 2010;2010:174378.

    Google Scholar 

  326. Rice J, Ottensmeier CH, Stevenson FK. DNA vaccines: precision tools for activating effective immunity against cancer. Nat Rev Cancer. 2008;8(2):108–20.

    CAS  PubMed  Google Scholar 

  327. Iurescia S, Fioretti D, Pierimarchi P, Signori E, Zonfrillo M, Tonon G, et al. Genetic immunization with CDR3-based fusion vaccine confers protection and long-term tumor-free survival in a mouse model of lymphoma. J Biomed Biotechnol. 2010;2010:316069.

    PubMed Central  PubMed  Google Scholar 

  328. Rinaldi M, Fioretti D, Iurescia S, Signori E, Pierimarchi P, Seripa D, et al. Anti-tumor immunity induced by CDR3-based DNA vaccination in a murine B-cell lymphoma model. Biochem Biophys Res Commun. 2008;370(2):279–84.

    CAS  PubMed  Google Scholar 

  329. Smith CM, Wilson NS, Waithman J, Villadangos JA, Carbone FR, Heath WR, et al. Cognate CD4+ T cell licensing of dendritic cells in CD8+ T cell immunity. Nat Immunol. 2004;5(11):1143–8.

    CAS  PubMed  Google Scholar 

  330. Wan YY, Flavell RA. How diverse—CD4 effector T cells and their functions. J Mol Cell Biol. 2009;1(1):20–36.

    PubMed Central  CAS  PubMed  Google Scholar 

  331. Hung K, Hayashi R, Lafond-Walker A, Lowenstein C, Pardoll D, Levitsky H. The central role of CD4+ T cells in the antitumor immune response. J Exp Med. 1998;188(12):2357–68.

    PubMed Central  CAS  PubMed  Google Scholar 

  332. Murphy KM, Travers P, Walport M. Janeway’s Immunobiology. 7th ed. New York: Garland Science Publishing; 2007.

    Google Scholar 

  333. Kim Y, Sette A, Peters B. Applications for T-cell epitope queries and tools in the Immune Epitope Database and Analysis Resource. J Immunol Methods. 2011;374(1):62–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  334. Rosa DS, Ribeiro SP, Cunha-Neto E. CD4+ T cell epitope discovery and rational vaccine design. Arch Immunol Ther Exp. 2010;58(2):121–30.

    CAS  Google Scholar 

  335. Houot R, Levy R. Vaccines for lymphomas: idiotype vaccines and beyond. Blood Rev. 2009;23(3):137–42.

    CAS  PubMed  Google Scholar 

  336. Rinaldi M, Ria F, Parrella P, Signori E, Serra A, Ciafrè SA, et al. Antibodies elicited by naked DNA vaccination against the complementary-determining region 3 hypervariable region of immunoglobulin heavy chain idiotypic determinants of B-lymphoproliferative disorders specifically react with patients’ tumor cells. Cancer Res. 2001;61(4):1555–62.

    CAS  PubMed  Google Scholar 

  337. Hansson L, Rabbani H, Fagerberg J, Österborg A, Mellstedt H. T-cell epitopes within the complementarity-determining and framework regions of the tumor-derived immunoglobulin heavy chain in multiple myeloma. Blood. 2003;101(12):4930–6.

    CAS  PubMed  Google Scholar 

  338. Harig S, Witzens M, Krackhardt AM, Trojan A, Barrett P, Broderick R, et al. Induction of cytotoxic T-cell responses against immunoglobulin V region–derived peptides modified at human leukocyte antigen–A2 binding residues. Blood. 2001;98(10):2999–3005.

    CAS  PubMed  Google Scholar 

  339. Terasawa H, Tsang K-Y, Gulley J, Arlen P, Schlom J. Identification and characterization of a human agonist cytotoxic T-lymphocyte epitope of human prostate-specific antigen. Clin Cancer Res. 2002;8(1):41–53.

    CAS  PubMed  Google Scholar 

  340. Borbulevych OY, Baxter TK, Yu Z, Restifo NP, Baker BM. Increased immunogenicity of an anchor-modified tumor-associated antigen is due to the enhanced stability of the peptide/MHC complex: implications for vaccine design. J Immunol. 2005;174(8):4812–20.

    PubMed Central  CAS  PubMed  Google Scholar 

  341. Williams BB, Wall M, Miao RY, Williams B, Bertoncello I, Kershaw MH, et al. Induction of T cell-mediated immunity using a c-Myb DNA vaccine in a mouse model of colon cancer. Cancer Immunol Immunother. 2008;57(11):1635–45.

    CAS  PubMed  Google Scholar 

  342. Link Snyder H, Bačík I, Yewdell JW, Behrens TW, Bennink JR. Promiscuous liberation of MHC‐class I‐binding peptides from the C termini of membrane and soluble proteins in the secretory pathway. Eur J Immunol. 1998;28(4):1339–46.

    CAS  Google Scholar 

  343. Signori E, Iurescia S, Massi E, Fioretti D, Chiarella P, De Robertis M, et al. DNA vaccination strategies for anti-tumour effective gene therapy protocols. Cancer Immunol Immunother. 2010;59(10):1583–91.

    CAS  PubMed  Google Scholar 

  344. Wenger C, Stern M, Herrmann R, Rochlitz C, Pless M. Rituximab plus gemcitabine: a therapeutic option for elderly or frail patients with aggressive non Hodgkin’s lymphoma? Leuk Lymphoma. 2005;46(1):71–5.

    CAS  PubMed  Google Scholar 

  345. El Gnaoui T, Dupuis J, Belhadj K, Jais J, Rahmouni A, Copie-Bergman C, et al. Rituximab, gemcitabine and oxaliplatin: an effective salvage regimen for patients with relapsed or refractory B-cell lymphoma not candidates for high-dose therapy. Ann Oncol. 2007;18(8):1363–8.

    PubMed  Google Scholar 

  346. Corazzelli G, Russo F, Capobianco G, Marcacci G, Della Cioppa P, Pinto A. Gemcitabine, ifosfamide, oxaliplatin and rituximab (R-GIFOX), a new effective cytoreductive/mobilizing salvage regimen for relapsed and refractory aggressive non-Hodgkin’s lymphoma: results of a pilot study. Ann Oncol. 2006;17 suppl 4:iv18–24.

    PubMed  Google Scholar 

  347. Smith S, Toor A, Klein J, Rodriguez T, Stiff P. The combination of gallium nitrate, rituximab and dexamethasone is effective and safe as a salvage regimen for diffuse large B-cell lymphoma. J Clin Oncol. 2006;24(June20Suppl):17510.

    Google Scholar 

  348. Leonard JP, Coleman M, Ketas J, Ashe M, Fiore JM, Furman RR, et al. Combination antibody therapy with epratuzumab and rituximab in relapsed or refractory non-Hodgkin’s lymphoma. J Clin Oncol. 2005;23(22):5044–51.

    CAS  PubMed  Google Scholar 

  349. Niitsu N, Kohuri M, Higashihara M, Bessho M. Phase II study of the CPT‐11, mitoxantrone and dexamethasone regimen in combination with rituximab in elderly patients with relapsed diffuse large B‐cell lymphoma. Cancer Sci. 2006;97(9):933–7.

    CAS  PubMed  Google Scholar 

  350. Younes A, McLaughlin P, Romaguera J, Hagemeister F, Pro B, Dang N et al., editors. Taxol plus topotecan plus rituximab (TTR) with G-CSF support: an effective salvage program for the treatment of patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma (NHL) who failed CHOP-like and platinum-based therapy. Blood. 2003;102(11):142A–3A.

    Google Scholar 

  351. Canales M, Sanjurjo M, García-Vela J, De Paz R, Cobo T, de la Guia A et al., editors. Paclitaxel and topotecan in combination with rituximab as effective second-line salvage regimen in resistant aggressive non-Hodgkin’s lymphoma. Ann Oncol. 2005;16:181.

    Google Scholar 

  352. Woehrer S, Hejna M, Skrabs C, Drach J, Zielinski CC, Jaeger U, et al. Rituximab, Ara-C, dexamethasone and oxaliplatin is safe and active in heavily pretreated patients with diffuse large B-cell lymphoma. Oncology. 2006;69(6):499–502.

    CAS  Google Scholar 

  353. Xia Z-G, Xu Z-Z, Zhao W-L, Zhao S-Q, Ding F, Chen Y, et al. The prognostic value of immunohistochemical subtyping in Chinese patients with de novo diffuse large B-cell lymphoma undergoing CHOP or R-CHOP treatment. Ann Hematol. 2010;89(2):171–7.

    CAS  PubMed  Google Scholar 

  354. Saito B, Shiozawa E, Usui T, Nakashima H, Maeda T, Hattori N, et al. Rituximab with chemotherapy improves survival of non-germinal center type untreated diffuse large B-cell lymphoma. Leukemia. 2007;21(12):2563–6.

    CAS  PubMed  Google Scholar 

  355. Fu K, Weisenburger DD, Choi WW, Perry KD, Smith LM, Shi X, et al. Addition of rituximab to standard chemotherapy improves the survival of both the germinal center B-cell–like and non–germinal center B-cell–like subtypes of diffuse large B-cell lymphoma. J Clin Oncol. 2008;26(28):4587–94.

    CAS  PubMed  Google Scholar 

  356. Czuczman MS, Fayad L, Delwail V, Cartron G, Jacobsen E, Kuliczkowski K, et al. Ofatumumab monotherapy in rituximab-refractory follicular lymphoma: results from a multicenter study. Blood. 2012;119(16):3698–704.

    CAS  PubMed  Google Scholar 

  357. Czuczman MS, Hess G, Gadeberg OV, Pedersen LM, Goldstein N, Gupta I, et al. Chemoimmunotherapy with ofatumumab in combination with CHOP in previously untreated follicular lymphoma. Br J Haematol. 2012;157(4):438–45.

    CAS  PubMed  Google Scholar 

  358. Carlile D, Meneses-Lorente G, Wassner-Fritsch E, Hourcade-Potelleret F, Wenger MK, Cartron G et al., editors. Pharmacokinetics of obinutuzumab (GA101) in patients with CD20+ relapsed/refractory malignant disease receiving concomitant chemotherapy (Phase Ib Study BO21000). Blood. 2011;Abs 374.

    Google Scholar 

  359. Friedberg JW VJ, Kahl BS, Brunvand M, Goy A, Kasamon Y, Brington B, Li J, Ho W, Cheson BD. A Phase I Study of PRO131921, a novel anti-CD20 monoclonal antibody in patients with relapsed/refractory CD20+ Indolent NHL: correlation between clinical responses and AUC pharmacokinetics. ASH annual meeting abstract. 2009(114):3472.

    Google Scholar 

  360. Wayne JL, Ganjoo KN, Pohlman BL, De Vos S, Flinn IW, Dang NH et al., editors. Efficacy of ocaratuzumab (AME-133v) in relapsed follicular lymphoma patients refractory to prior rituximab. J Clin Oncol. 2012;30(15):2318.

    Google Scholar 

  361. Kim Y, Ponomarenko J, Zhu Z, Tamang D, Wang P, Greenbaum J, et al. Immune epitope database analysis resource. 2012(40):525–30.

    Google Scholar 

  362. Vita R, Zarebski L, Greenbaum JA, Emami H, Hoof I, Salimi N, et al. The immune epitope database 2.0. 2010;38:854–62.

    Google Scholar 

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Ebadi, M., Reddy, N.M., Rezaei, N. (2015). Immunopathology and Immunotherapy of Non-Hodgkin Lymphoma. In: Rezaei, N. (eds) Cancer Immunology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-46410-6_8

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