Advertisement

International Journal of Hematology

, Volume 77, Issue 5, pp 444–455 | Cite as

Immunotherapy for Lymphomas

  • John M. TimmermanEmail author
Progress in Hematology

Abstract

A growing list of immunotherapeutic strategies is now being employed to combat lymphoid malignancies. These efforts are warranted given that B-cell lymphomas, particularly those of the common follicular subtype, are among the most “immune-responsive” of all human cancers. Although systemic cytokine therapies for B-cell malignancies have been largely disappointing to date, monoclonal antibody therapies, principally the anti-CD20 antibody rituximab, have already made enormous impact on the treatment algorithm for many B-cell lymphomas. Therapeutic vaccines targeting the tumor-specific immunoglobulin idiotype have demonstrated promising results against lymphomas in phase I/II studies and are currently being evaluated in phase III randomized trials. Additional vaccine therapies being developed include those based on dendritic cells, recombinant idiotype proteins, DNA, heat shock proteins, and gene-modified tumor cells. It is hoped that immunotherapeutic agents, used in tandem or in combination, may someday allow effective treatment of lymphoid malignancies and delay or even replace the need for conventional cytotoxic therapies.Int J Hematol. 2003;77:444-455.

Key words

Lymphoma Immunotherapy Vaccines Idiotype 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Horning SJ, Rosenberg SA. The natural history of initially untreated low-grade non-Hodgkin’s lymphomas.N Engl J Med. 1984;311:1471–1475.CrossRefPubMedGoogle Scholar
  2. 2.
    Biologic response modifiers: a report.Natl Cancer Inst Monogr. 1983;63:57–59.Google Scholar
  3. 3.
    Fefer A. Interleukin-2: clinical applications—hematologic malignancies. In: Rosenberg SA, ed.Principles and Practice of the Biologic Therapy of Cancer. 3rd ed. Philadelphia: Lippincott Williams &Wilkins; 2000:83–92.Google Scholar
  4. 4.
    Davis TA, Maloney DG, Czerwinski DK, Liles TM, Levy R. Anti-idiotype antibodies can induce long term complete remissions in non-Hodgkin’s lymphoma patients without eradicating the malignant clone.Blood. 1998;92:1184–1190.PubMedGoogle Scholar
  5. 5.
    McLaughlin P, Grillo-Lopez AJ, Link BK, 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;16:2825–2833.CrossRefPubMedGoogle Scholar
  6. 6.
    Timmerman JM, Levy R. The history of the development of vaccines for lymphoma.Clin Lymphoma. 2000;1:129–139.CrossRefPubMedGoogle Scholar
  7. 7.
    Talpaz M, Ravandi F, Kurzock R, Estrov Z, Kantarjian HM. Inter-feron-alpha and beta: clinical applications—leukemias, lymphomas, and multiple myeloma. In: Rosenberg SA, ed:Principles and Practice of the Biologic Therapy of Cancer. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2000:209–224.Google Scholar
  8. 8.
    Allen IE, Ross SD, Borden SP, et al. Meta-analysis to assess the efficacy of interferon-alpha in patients with follicular non-Hodgkin’s lymphoma.J Immunother. 2001;24:58–65.CrossRefPubMedGoogle Scholar
  9. 9.
    Rohatiner A, Radford J, Deakin D, et al. A randomized controlled trial to evaluate the role of interferon as initial and maintenance therapy in patients with follicular lymphoma.Br J Cancer. 2001;85: 29–35.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Fritz E, Ludwig H. Interferon-alpha treatment in multiple myeloma: meta-analysis of 30 randomised trials among 3948 patients.Ann Oncol. 2000;11:1427–1436.CrossRefPubMedGoogle Scholar
  11. 11.
    Gisselbrecht C, Maraninchi D, Pico JL, et al. Interleukin-2 treatment in lymphoma: a phase II multicenter study.Blood. 1994;83: 2081–2085.PubMedGoogle Scholar
  12. 12.
    Rosenberg SA, Yang JC, Schwartzentruber DJ, et al. Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma.Nat Med. 1998;4: 321–327.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Shimizu K, Fields RC, Giedlin M, Mule JJ. Systemic administration of interleukin 2 enhances the therapeutic efficacy of dendritic cell-based tumor vaccines.Proc Natl Acad Sci USA. 1999;96:2268–2273.CrossRefPubMedGoogle Scholar
  14. 14.
    Colombo MP, Trinchieri G. Interleukin-12 in anti-tumor immunity and immunotherapy.Cytokine Growth Factor Rev. 2002;13:155–168.CrossRefPubMedGoogle Scholar
  15. 15.
    Younes A, Robertson MJ, Flinn I, et al. A phase II study of interleukin-12 in patients with relapsed non-Hodgkin lymphoma and Hodgkin’s disease [abstract].Blood. 2002;100:364a. Abstract 1408.CrossRefGoogle Scholar
  16. 16.
    Ansell SM, Witzig TE, Kurtin PJ, et al. Phase 1 study of interleukin-12 in combination with rituximab in patients with B-cell non-Hodgkin lymphoma.Blood. 2002;99:67–74.CrossRefPubMedGoogle Scholar
  17. 17.
    Gajewski TF, Fallarino F, Ashikari A, Sherman M. Immunization of HLA-A2+ melanoma patients with MAGE-3 or MelanA peptide-pulsed autologous peripheral blood mononuclear cells plus recombinant human interleukin 12.Clin Cancer Res. 2001;7:895s-901s.PubMedGoogle Scholar
  18. 18.
    Gong J, Koido S, Chen D, et al. Immunization against murine multiple myeloma with fusions of dendritic and plasmacytoma cells is potentiated by interleukin 12.Blood. 2002;99:2512–2517.CrossRefPubMedGoogle Scholar
  19. 19.
    Curti A, Parenza M, Colombo MP. Autologous and MHC class I-negative allogeneic tumor cells secreting IL-12 together cure disseminated A20 lymphoma.Blood. 2003;101:568–575.CrossRefPubMedGoogle Scholar
  20. 20.
    Rosen ST, ed. Current and ongoing clinical development of immunotherapy in B cell malignancies.Semin Oncol. 2002; 29(suppl 2):1–124.CrossRefPubMedGoogle Scholar
  21. 21.
    Linenberger ML, Maloney DG, Bernstein ID. Antibody-directed therapies for hematological malignancies.Trends Mol Med. 2002; 8:69–76.CrossRefPubMedGoogle Scholar
  22. 22.
    Stevenson GT, Elliott EV, Stevenson FK. Idiotypic determinants on the surface immunoglobulin of neoplastic lymphocytes: a therapeutic target.Fed Proc. 1977;36:2268–2271.PubMedGoogle Scholar
  23. 23.
    Hall SS. “Dr.Levy’s Favorite Guinea Pig”: A Commotion in the Blood. New York: Henry Holt; 1997:391–408.Google Scholar
  24. 24.
    Levy R, Dilley J. Rescue of immunoglobulin secretion from human neoplastic lymphoid cells by somatic cell hybridization.Proc Natl Acad Sci USA. 1978;75:2411–2415.CrossRefPubMedGoogle Scholar
  25. 25.
    Miller RA, Maloney DG, Warnke R, Levy R. Treatment of B-cell lymphoma with monoclonal anti-idiotype antibody.N Engl J Med. 1982;306:517–522.CrossRefPubMedGoogle Scholar
  26. 26.
    Maloney DG. Monoclonal antibodies. In: Mendelsohn J, Howley P, Israel M, Liotta L, eds.The Molecular Basis of Cancer. 2nd ed. Philadelphia: WB Saunders; 2001:467–501.Google Scholar
  27. 27.
    Reff ME, Carner K, Chambers KS, et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20.Blood. 1994;83:435–445.PubMedGoogle Scholar
  28. 28.
    Maloney DG, Smith B, Rose A. Rituximab: mechanism of action and resistance.Semin Oncol. 2002;29(suppl 2):2–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Clynes RA, Towers TL, Presta LG, Ravetch JV. Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets.Nat Med. 2000;6:443–446.CrossRefPubMedGoogle Scholar
  30. 30.
    Weng WK, Levy R. Expression of complement inhibitors CD46, CD55, and CD59 on tumor cells does not predict clinical outcome after rituximab treatment in follicular non-Hodgkin lymphoma.Blood. 2001;98:1352–1357.CrossRefPubMedGoogle Scholar
  31. 31.
    Cartron G, Dacheux L, Salles G, et al. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene.Blood. 2002;99:754–758.CrossRefPubMedGoogle Scholar
  32. 32.
    Davis TA, Maloney DG, Grillo-Lopez AJ, et al. Combination immunotherapy of relapsed or refractory low-grade or follicular non-Hodgkin’s lymphoma with rituximab and interferon-alpha-2a.Clin Cancer Res. 2000;6:2644–2652.PubMedGoogle Scholar
  33. 33.
    Friedberg JW, Neuberg D, Gribben JG, et al. Combination immunotherapy with rituximab and interleukin 2 in patients with relapsed or refractory follicular non-Hodgkin’s lymphoma.Br J Haematol. 2002;117:828–834.CrossRefPubMedGoogle Scholar
  34. 34.
    Warren TL, Weiner GJ. Synergism between cytosine-guanine oligodeoxynucleotides and monoclonal antibody in the treatment of lymphoma.Semin Oncol. 2002;29(suppl 2):93–97.CrossRefPubMedGoogle Scholar
  35. 35.
    Leonard JP, Link BK. Immunotherapy of non-Hodgkin’s lymphoma with hLL2 (epratuzumab, an anti-CD22 monoclonal antibody) and Hu1D10 (apolizumab).Semin Oncol. 2002;29(suppl 2):81–86.CrossRefPubMedGoogle Scholar
  36. 36.
    Leonard JP, Coleman M, Matthews JC, et al. Phase I/II trial of Epratuzumab (humanized anti-CD22 antibody) in non-Hodgkin’s lymphoma (NHL) [abstract].Blood. 2002;100:358a. Abstract 1388.Google Scholar
  37. 37.
    Keating MJ, Flinn I, Jain V, et al. Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study.Blood. 2002;99:3554–3561.CrossRefPubMedGoogle Scholar
  38. 38.
    Hopkins M, Pathan N, Chu P, Grint P, Saven A. IDEC-152 (Anti- CD23) triggers apoptosis of chronic lymphocytic leukemia (CLL) cells in vitro [abstract].Blood. 2002;100:597a. Abstract 2346.Google Scholar
  39. 39.
    Czuczman M, Witzig TE, Younes A, et al. IDEC-114, an anti-CD80 monoclonal antibody for relapsed of refractory, follicular NHL: phase I/II study of safety, efficacy, and pharmacokinetics [abstract].Blood. 2002;100:163a. Abstract 610.Google Scholar
  40. 40.
    Nagy ZA, Hubner B, Lohning C, et al. Fully human, HLA-DR- specific monoclonal antibodies efficiently induce programmed death of malignant lymphoid cells.Nat Med. 2002;8:801–807.CrossRefPubMedGoogle Scholar
  41. 41.
    French RR, Chan HT,Tutt AL, Glennie MJ. CD40 antibody evokes a cytotoxic T-cell response that eradicates lymphoma and bypasses T-cell help.Nat Med. 1999;5:548–553.CrossRefPubMedGoogle Scholar
  42. 42.
    Tutt AL, O’Brien L, Hussain A, Crowther GR, French RR, Glennie MJ. T cell immunity to lymphoma following treatment with anti-CD40 monoclonal antibody.J Immunol. 2002;168:2720–2728.CrossRefPubMedGoogle Scholar
  43. 43.
    van Mierlo GJ, den Boer AT, Medema JP, et al. CD40 stimulation leads to effective therapy of CD40(-) tumors through induction of strong systemic cytotoxic T lymphocyte immunity.Proc Natl Acad Sci USA. 2002;99:5561–5566.CrossRefPubMedGoogle Scholar
  44. 44.
    Sotomayor EM, Borrello I, Tubb E, et al. Conversion of tumor-specific CD4+ T-cell tolerance to T-cell priming through in vivo ligation of CD40.Nat Med. 1999;5:780–787.CrossRefPubMedGoogle Scholar
  45. 45.
    Vonderheide RH, Dutcher JP, Anderson JE, et al. Phase I study of recombinant human CD40 ligand in cancer patients.J Clin Oncol. 2001;19:3280–3287.CrossRefPubMedGoogle Scholar
  46. 46.
    Kwak LW, Campbell MJ, Czerwinski DK, Hart S, Miller RA, Levy R. Induction of immune responses in patients with B-cell lymphoma against the surface-immunoglobulin idiotype expressed by their tumors.N Engl J Med. 1992;327:1209–1215.CrossRefPubMedGoogle Scholar
  47. 47.
    Hsu FJ, Caspar CB, Czerwinski D, et al. Tumor-specific idiotype vaccines in the treatment of patients with B-cell lymphoma: long-term results of a clinical trial.Blood. 1997;89:3129–3135.PubMedGoogle Scholar
  48. 48.
    Banchereau J, Briere F, Caux C, et al. Immunobiology of dendritic cells.Annu Rev Immunol. 2000;18:767–811.CrossRefPubMedGoogle Scholar
  49. 49.
    Timmerman JM, Levy R. Dendritic cell vaccines for cancer immunotherapy.Annu Rev Med. 1999;50:507–529.CrossRefPubMedGoogle Scholar
  50. 50.
    Hsu FJ, Benike C, Fagnoni F, et al. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells.Nat Med. 1996;2:52–58.CrossRefPubMedGoogle Scholar
  51. 51.
    Timmerman JM, Czerwinski DK, Davis TA, et al. Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: clinical and immune responses in 35 patients.Blood. 2002;99:1517–1526.CrossRefPubMedGoogle Scholar
  52. 52.
    Kwak LW, Young HA, Pennington RW, Weeks SD. Vaccination with syngeneic, lymphoma-derived immunoglobulin idiotype combined with granulocyte/macrophage colony-stimulating factor primes mice for a protective T-cell response.Proc Natl Acad Sci USA. 1996;93:10972–10977.CrossRefPubMedGoogle Scholar
  53. 53.
    Bendandi M, Gocke CD, Kobrin CB, et al. Complete molecular remissions induced by patient-specific vaccination plus granulo- cyte-monocyte colony-stimulating factor against lymphoma.Nat Med. 1999;5:1171–1177.CrossRefPubMedGoogle Scholar
  54. 54.
    Wilson WH, Neelapu S, White T, et al. Idiotype vaccine following EPOCH-Rituximab treatment in untreated mantle cell lymphoma [abstract].Blood. 2002;100:162a. Abstract 608.Google Scholar
  55. 55.
    Timmerman JM, Czerwinski D, Taid B, et al. A phase I/II trial to evaluate the immunogenicity of recombinant idiotype protein vaccines for the treatment of non-Hodgkin’s lymphoma (NHL).Blood. 2000;96:578a.Google Scholar
  56. 56.
    Timmerman J, Vose J, Kunkel L, et al. A phase 2 study demonstrating recombinant idiotype vaccine elicits specific anti-idiotype immune responses in aggressive non-Hodgkin’s lymphoma [abstract].Blood. 2001;98:341a. Abstract 1440.Google Scholar
  57. 57.
    Redfern C, Guthrie TH, Smith MR, et al. A phase I trial of FavId (Id-KLH) for relapsed indolent non-Hodgkin’s lymphoma [abstract].Blood. 2002;100:357a. Abstract 1383.Google Scholar
  58. 58.
    McCormick AA, Kumagai MH, Hanley K, et al. Rapid production of specific vaccines for lymphoma by expression of the tumor-derived single-chain Fv epitopes in tobacco plants.Proc Natl Acad Sci USA. 1999;96:703–708.CrossRefPubMedGoogle Scholar
  59. 59.
    Reddy SA, Czerwinski DK, Rajapaksa R, et al. Plant derived single chain Fv idiotype vaccines are safe and immunogenic in patients with follicular lymphoma: results of a phase I study [abstract].Blood. 2002;100:163a. Abstract 609.Google Scholar
  60. 60.
    Osterroth F, Garbe A, Fisch P, Veelken H. Stimulation of cytotoxic T cells against idiotype immunoglobulin of malignant lymphoma with protein-pulsed or idiotype-transduced dendritic cells.Blood. 2000;95:1342–1349.PubMedGoogle Scholar
  61. 61.
    Veelken H, Mauerer K, Waller CF, Eckerman E, Simon F, Osterroth F. A phase I trial of a recombinant idiotype vaccine for active immunization against refractory NHL [abstract].Ann Oncol. 2002; 13:40.Abstract 120.Google Scholar
  62. 62.
    Restifo NP, Ying H, Hwang L, Leitner WW. The promise of nucleic acid vaccines.Gene Ther. 2000;7:89–92.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Krieg AM, Yi AK, Hartmann G. Mechanisms and therapeutic applications of immune stimulatory CpG DNA.Pharmacol Ther. 1999;84:113–120.CrossRefPubMedGoogle Scholar
  64. 64.
    Syrengelas AD, Chen TT, Levy R. DNA immunization induces protective immunity against B-cell lymphoma.Nat Med. 1996;2: 1038–1041.CrossRefPubMedGoogle Scholar
  65. 65.
    King CA, Spellerberg MB, Zhu D, et al. DNA vaccines with single- chain Fv fused to fragment C of tetanus toxin induce protective immunity against lymphoma and myeloma.Nat Med. 1998;4: 1281–1286.CrossRefPubMedGoogle Scholar
  66. 66.
    Biragyn A, Tani K, Grimm MC, Weeks S, Kwak LW. Genetic fusion of chemokines to a self tumor antigen induces protective, T-cell dependent antitumor immunity.Nat Biotechnol. 1999;17:253–258.CrossRefPubMedGoogle Scholar
  67. 67.
    Timmerman JM, Singh G, Hermanson G, et al. Immunogenicity of a plasmid DNA vaccine encoding chimeric idiotype in patients with B-cell lymphoma.Cancer Res. 2002;62:5845–5852.PubMedGoogle Scholar
  68. 68.
    Zhu D, Rice J, Savelyeva N, Stevenson FK. DNA fusion vaccines against B-cell tumors.Trends Mol Med. 2001;7:566–572.CrossRefPubMedGoogle Scholar
  69. 69.
    Biragyn A, Surenhu M, Yang D, et al. Mediators of innate immunity that target immature, but not mature, dendritic cells induce antitumor immunity when genetically fused with nonimmunogenic tumor antigens.J Immunol. 2001;167:6644–6653.CrossRefPubMedGoogle Scholar
  70. 70.
    Dranoff G, Jaffee E, Lazenby A, et al. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long- lasting anti-tumor immunity.Proc Natl Acad Sci USA. 1993;90:3539–3543.CrossRefPubMedGoogle Scholar
  71. 71.
    Pardoll DM. Cancer vaccines.Nat Med. 1998;4:525–531.CrossRefPubMedGoogle Scholar
  72. 72.
    Soiffer R, Lynch T, Mihm M, et al. Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma.Proc Natl Acad Sci USA. 1998;95:13141–13146.CrossRefPubMedGoogle Scholar
  73. 73.
    Simons JW, Jaffee EM, Weber CE, et al. Bioactivity of autologous irradiated renal cell carcinoma vaccines generated by ex vivo granulocyte-macrophage colony-stimulating factor gene transfer.Cancer Res. 1997;57:1537–1546.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Nemunaitis J, Sterman D, Jablons D, et al. A phase I/II study of autologous GM-CSF gene-modified cancer vaccines in subjects with non-small cell lung cancer [abstract].Proc Am Soc Clin Oncol. 2001;20:254a. Abstract 1019.Google Scholar
  75. 75.
    Levitsky HI, Montgomery J, Ahmadzadeh M, et al. Immunization with granulocyte-macrophage colony-stimulating factor-transduced, but not B7-1-transduced, lymphoma cells primes idiotype-specific T cells and generates potent systemic antitumor immunity.J Immunol. 1996;156:3858–3865.PubMedGoogle Scholar
  76. 76.
    Borrello I, Sotomayor EM, Rattis FM, Cooke SK, Gu L, Levitsky HI. Sustaining the graft-versus-tumor effect through post-transplant immunization with granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing tumor vaccines.Blood. 2000;95:3011–3019.PubMedGoogle Scholar
  77. 77.
    Borrello I, Sotomayor EM, Cooke S, Levitsky HI. A universal granulocyte-macrophage colony-stimulating factor-producing bystander cell line for use in the formulation of autologous tumor cell-based vaccines.Hum Gene Ther. 1999;10:1983–1991.CrossRefPubMedGoogle Scholar
  78. 78.
    Borrello IM, Sotomayor EM. Cancer vaccines for hematologic malignancies.Cancer Control. 2002;9:138–151.CrossRefPubMedGoogle Scholar
  79. 79.
    Gordon J, Pound JD. Fortifying B cells with CD154: an engaging tale of many hues.Immunology. 2000;100:269–280.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Wierda WG, Cantwell MJ, Woods SJ, Rassenti LZ, Prussak CE, Kipps TJ. CD40-ligand (CD154) gene therapy for chronic lymphocytic leukemia.Blood. 2000;96:2917–2924.PubMedGoogle Scholar
  81. 81.
    Kato K, Cantwell MJ, Sharma S, Kipps TJ. Gene transfer of CD40- ligand induces autologous immune recognition of chronic lymphocytic leukemia B cells.J Clin Invest. 1998;101:1133–1141.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Przepiorka D, Srivastava PK. Heat shock protein-peptide complexes as immunotherapy for human cancer.Mol Med Today. 1998; 4:478–484.CrossRefPubMedGoogle Scholar
  83. 83.
    Antigenics Inc. Available at: www.antigenics.com.Google Scholar
  84. 84.
    Steinman RM, Dhodapkar M. Active immunization against cancer with dendritic cells: the near future.Int J Cancer. 2001;94:459–473.CrossRefPubMedGoogle Scholar
  85. 85.
    Selenko N, Maidic O, Draxier S, et al. CD20 antibody (C2B8)- induced apoptosis of lymphoma cells promotes phagocytosis by dendritic cells and cross-priming of CD8+ cytotoxic T cells.Leukemia. 2001;15:1619–1626.CrossRefPubMedGoogle Scholar
  86. 86.
    Dhodapkar KM, Krasovsky J, Williamson B, Dhodapkar MV. Anti-tumor monoclonal antibodies enhance cross-presentation of cellular antigens and the generation of myeloma-specific killer T cells by dendritic cells.J Exp Med. 2002;195:125–133.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Rosenberg SA. A new era for cancer immunotherapy based on the genes that encode cancer antigens.Immunity. 1999;10:281–287.CrossRefPubMedGoogle Scholar
  88. 88.
    Campbell MJ, Carroll W, Kon S, et al. Idiotype vaccination against murine B cell lymphoma: humoral and cellular responses elicited by tumor-derived immunoglobulin M and its molecular subunits.J Immunol. 1987;139:2825–2833.PubMedGoogle Scholar
  89. 89.
    George AJ, Tutt AL, Stevenson FK. Anti-idiotypic mechanisms involved in suppression of a mouse B cell lymphoma, BCL1.J Immunol. 1987;138:628–634.PubMedGoogle Scholar
  90. 90.
    Timmerman JM, Levy R. Linkage of foreign carrier protein to a self-tumor antigen enhances the immunogenicity of a pulsed dendritic cell vaccine.J Immunol. 2000;164:4797–4803.CrossRefPubMedGoogle Scholar
  91. 91.
    van der Kolk LE, Baars JW, Prins MH, van Oers MH. Rituximab treatment results in impaired secondary humoral immune responsiveness.Blood. 2002;100:2257–2259.Google Scholar
  92. 92.
    Gonzalez-Stawinski GV, Yu PB, Love SD, Parker W, Davis RD Jr. Hapten-induced primary and memory humoral responses are inhibited by the infusion of anti-CD20 monoclonal antibody (IDEC-C2B8, rituximab).Clin Immunol. 2001;98:175–179.CrossRefPubMedGoogle Scholar
  93. 93.
    Qin Z, Richter G, Schuler T, Ibe S, Cao X, Blankenstein T. B cells inhibit induction of T cell-dependent tumor immunity.Nat Med. 1998;4:627–630.CrossRefPubMedGoogle Scholar
  94. 94.
    Timmerman JM. Vaccine therapies for non-Hodgkin’s lymphoma.Curr Treat Options Oncol. 2002;3:307–315.CrossRefPubMedGoogle Scholar
  95. 95.
    Ruffini PA, Neelapu SS, Kwak LW, Biragyn A. Idiotypic vaccination for B-cell malignancies as a model for therapeutic cancer vaccines: from prototype protein to second generation vaccines.Haematologica. 2002;87:989–1001.PubMedGoogle Scholar
  96. 96.
    Okada CY, Wong CP, Denney DW, Levy R. TCR vaccines for active immunotherapy of T cell malignancies.J Immunol. 1997;159: 5516–5527.PubMedGoogle Scholar
  97. 97.
    Wong CP, Okada CY, Levy R. TCR vaccines against T cell lymphoma: QS-21 and IL-12 adjuvants induce a protective CD8+ T cell response.J Immunol. 1999;162:2251–2258.PubMedGoogle Scholar
  98. 98.
    Hooijberg E, Visseren MJ, van den Berk PC, et al. Lysis of syn-geneic tumor B cells by autoreactive cytotoxic T lymphocytes specific for a CD19 antigen-derived synthetic peptide.J Immunother Emphasis Tumor Immunol. 1996;19:346–356.CrossRefPubMedGoogle Scholar
  99. 99.
    Roberts WK, Livingston PO, Agus DB, Pinilla-Ibarz J, Zelenetz A, Scheinberg DA. Vaccination with CD20 peptides induces a biologically active, specific immune response in mice.Blood. 2002;99: 3748–3755.CrossRefPubMedGoogle Scholar
  100. 100.
    van der Bruggen P, Traversari C, Chomez P, et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma.Science. 1991;254:1643–1647.CrossRefPubMedGoogle Scholar
  101. 101.
    Chouaib S, Asselin-Paturel C, Mami-Chouaib F, Caignard A, Blay JY. The host-tumor immune conflict: from immunosuppression to resistance and destruction.Immunol Today. 1997;18: 493–497.CrossRefPubMedGoogle Scholar
  102. 102.
    Overwijk WW, Restifo NP. Creating therapeutic cancer vaccines: notes from the battlefield.Trends Immunol. 2001;22:5–7.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2003

Authors and Affiliations

  1. 1.Division of Hematology/OncologyUniversity of CaliforniaLos AngelesUSA

Personalised recommendations