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Modulation of tumor immunity by therapeutic monoclonal antibodies

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Abstract

The surveillance of tumors by the immune system of cancer patients and its impact on disease progression and patient survival have been largely documented over the last years. In parallel, the use of therapeutic monoclonal antibodies (mAbs) in oncology has gained a widespread recognition as it has made it possible to increase patient survival and to ameliorate the quality of life in a number of cancers. However, the clinical responses observed following mAb treatment remain largely heterogeneous and their duration is still highly unpredictable. Recently, the concept that the injection of therapeutic antibodies not only triggers early anti-tumor events such as receptor blockade, cytostasis, apoptosis, complement-dependent cytotoxicity and/or antibody-dependent cytotoxicity but also allows the host immune system to fight tumor cells through the development of a long-lasting adaptive immunity has emerged. In the present review, we will examine the arguments that support this concept by detailing the cellular and molecular events likely to underlie the induction of an efficient anti-tumor adaptive immune response by mAbs. We will also discuss the consequences of this induction on the way therapeutic antibodies can be used and inserted in a more global immunotherapeutic approach aiming at strengthening the adaptive anti-tumor immune response developed by cancer patients.

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References

  1. Klein, G. (1973). Epstein–Barr virus (EBV)-induced transformation of human lymphoid cells and immunosurveillance against lymphoma development. Annales d’Immunologie (Paris), 124, 391–405.

    CAS  Google Scholar 

  2. World Health Organization (1987) Genital human papillomavirus infections and cancer: memorandum from a WHO meeting. Bulletin of the World Health Organization 65: 817–827

  3. Pagès, F., Berger, A., Camus, M., Sanchez-Cabo, F., Costes, A., Molidor, R., et al. (2005). Effector memory T cells, early metastasis, and survival in colorectal cancer. The New England Journal of Medicine, 353, 2654–2666.

    PubMed  Google Scholar 

  4. Galon, J., Costes, A., Sanchez-Cabo, F., Kirilovsky, A., Mlecnik, B., Lagorce-Pagès, C., et al. (2006). Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science, 313, 1960–1964.

    PubMed  CAS  Google Scholar 

  5. Dieu-Nosjean, M.-C., Antoine, M., Danel, C., Heudes, D., Wislez, M., Poulot, V., et al. (2008). Long-term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures. Journal of Clinical Oncology, 26, 4410–4417.

    PubMed  CAS  Google Scholar 

  6. Türeci, O., Sahin, U., & Pfreundschuh, M. (1997). Serological analysis of human tumor antigens: molecular definition and implications. Molecular Medicine Today, 3, 342–349.

    PubMed  Google Scholar 

  7. Chen, Y. T., Scanlan, M. J., Sahin, U., Türeci, O., Gure, A. O., Tsang, S., et al. (1997). A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proceedings of the National Academy of Sciences of the United States of America, 94, 1914–1918.

    PubMed  CAS  Google Scholar 

  8. Boon, T., Coulie, P. G., van den Eynde, B. J., & van der Bruggen, P. (2006). Human T cell responses against melanoma. Annual Review of Immunology, 24, 175–208.

    PubMed  CAS  Google Scholar 

  9. Glennie, M. J., French, R. R., Cragg, M. S., & Taylor, R. P. (2007). Mechanisms of killing by anti-CD20 monoclonal antibodies. Molecular Immunology, 44, 3823–3837.

    PubMed  CAS  Google Scholar 

  10. Abès, R., Dutertre, C. A., Agnelli, L., & Teillaud, J. L. (2009). Activating and inhibitory Fcgamma receptors in immunotherapy: being the actor or being the target. Expert Review of Clinical Immunology, 5, 735–747.

    PubMed  Google Scholar 

  11. Takai, T., Li, M., Sylvestre, D., Clynes, R., & Ravetch, J. V. (1994). FcR gamma chain deletion results in pleiotrophic effector cell defects. Cell, 76, 519–529.

    PubMed  CAS  Google Scholar 

  12. Clynes, R. A., Towers, T. L., Presta, L. G., & Ravetch, J. V. (2000). Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Natural Medicines, 6, 443–446.

    CAS  Google Scholar 

  13. Zhang, Z., Zhang, M., Goldman, C. K., Ravetch, J. V., & Waldmann, T. A. (2003). Effective therapy for a murine model of adult T-cell leukemia with the humanized anti-CD52 monoclonal antibody, Campath-1H. Cancer Research, 63, 6453–6457.

    PubMed  CAS  Google Scholar 

  14. Zhang, M., Zhang, Z., Garmestani, K., Goldman, C. K., Ravetch, J. V., Brechbiel, M. W., et al. (2004). Activating Fc receptors are required for antitumor efficacy of the antibodies directed toward CD25 in a murine model of adult T-cell leukemia. Cancer Research, 64, 5825–5829.

    PubMed  CAS  Google Scholar 

  15. Cartron, G., Dacheux, L., Salles, G., Solal-Celigny, P., Bardos, P., Colombat, P., et al. (2002). Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood, 99, 754–758.

    PubMed  CAS  Google Scholar 

  16. Weng, W. K., & Levy, R. (2003). Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. Journal of Clinical Oncology, 21, 3940–3947.

    PubMed  CAS  Google Scholar 

  17. Ghielmini, M., Rufibach, K., Salles, G., Leoncini-Franscini, L., Léger-Falandry, C., Cogliatti, S., et al. (2005). Single agent rituximab in patients with follicular or mantle cell lymphoma: clinical and biological factors that are predictive of response and event-free survival as well as the effect of rituximab on the immune system: a study of the Swiss Group for Clinical Cancer Research (SAKK). Annals of Oncology, 16, 1675–1682.

    PubMed  CAS  Google Scholar 

  18. Treon, S. P., Hansen, M., Branagan, A. R., Verselis, S., Emmanouilides, C., Kimby, E., et al. (2005). Polymorphisms in FcgammaRIIIA (CD16) receptor expression are associated with clinical response to rituximab in Waldenstro m’s macroglobulinemia. Journal of Clinical Oncology, 23, 474–481.

    PubMed  CAS  Google Scholar 

  19. Kim, D. H., Jung, H. D., Kim, J. G., Lee, J. J., Yang, D. H., Park, Y. H., et al. (2006). FCGR3A gene polymorphisms may correlate with response to frontline R-CHOP therapy for diffuse large B-cell lymphoma. Blood, 108, 2720–2725.

    PubMed  CAS  Google Scholar 

  20. Zhang, W., Gordon, M., Schultheis, A. M., Yang, D. Y., Nagashima, F., Azuma, M., et al. (2007). FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab. Journal of Clinical Oncology, 25, 3712–3718.

    PubMed  CAS  Google Scholar 

  21. Musolino, A., Naldi, N., Bortesi, B., Pezzuolo, D., Capelletti, M., Missale, G., et al. (2008). Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER- 2/neu-positive metastatic breast cancer. Journal of Clinical Oncology, 26, 1789–1796.

    PubMed  CAS  Google Scholar 

  22. Lejeune, J., Thibault, G., Ternant, D., Cartron, G., Watier, H., & Ohresser, M. (2008). Evidence for linkage disequilibrium between Fcgamma RIIIa-V158F and Fcgamma RIIa-H131R polymorphisms in white patients, and for an Fcgamma RIIIa-restricted influence on the response to therapeutic antibodies. Journal of Clinical Oncology, 26, 5489–5491.

    PubMed  Google Scholar 

  23. Bibeau, F., Lopez-Crapez, E., Di Fiore, F., Thezenas, S., Ychou, M., Blanchard, F., et al. (2009). Impact of FcgammaRIIa- FcgammaRIIIa polymorphism and KRAS mutations on the clinical outcome of patients with metastatic colorectal cancer treated with cetuximab plus Irinotecan. Journal of Clinical Oncology, 27, 1122–1129.

    PubMed  CAS  Google Scholar 

  24. Miller, R. A., Maloney, D. G., Warnke, R., & Levy, R. (1982). Treatment of B-cell lymphoma with monoclonal anti-idiotype antibody. The New England Journal of Medicine, 306, 517–522.

    PubMed  CAS  Google Scholar 

  25. Rankin, E. M., Hekman, A., Somers, R., & Ten Bokkel Huinink, W. (1985). Treatment of two patients with B cell lymphoma with monoclonal anti-idiotype antibodies. Blood, 65, 1373–1381.

    PubMed  CAS  Google Scholar 

  26. Tao, M. H., & Levy, R. (1993). Idiotype/granulocyte-macrophage colony-stimulating factor fusion protein as a vaccine for B-cell lymphoma. Nature, 362, 755–758.

    PubMed  CAS  Google Scholar 

  27. Koprowski, H., Herlyn, D., Lubeck, M., DeFreitas, E., & Sears, H. F. (1984). Human anti-idiotype antibodies in cancer patients: is the modulation of the immune response beneficial for the patient? Proceedings of the National Academy of Sciences of the United States of America, 81, 216–219.

    PubMed  CAS  Google Scholar 

  28. Fournier, E., Sibéril, S., Costes, A., Varin, A., Fridman, W.-H., Teillaud, J.-L., et al. (2008). Activation of human peripheral IgM+ B cells is transiently inhibited by BCR-independent aggregation of Fc gamma RIIB. Journal of Immunology, 181, 5350–5359.

    CAS  Google Scholar 

  29. Regnault, A., Lankar, D., Lacabanne, V., Rodriguez, A., Théry, C., Rescigno, M., et al. (1999). Fcgamma receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalization. The Journal of Experimental Medicine, 189, 371–380.

    PubMed  CAS  Google Scholar 

  30. Amigorena, A., & Bonnerot, C. (1999). Fc receptors for IgG and antigen presentation on MHC class I and class II molecules. Seminars in Immunology, 11, 385–390.

    PubMed  CAS  Google Scholar 

  31. Bolland, S., & Ravetch, J. V. (2000). Spontaneous autoimmune disease in Fc(gamma)RIIB-deficient mice results from strain-specific epistasis. Immunity, 13, 277–285.

    PubMed  CAS  Google Scholar 

  32. Nimmerjahn, F., & Ravetch, J. V. (2008). Fcgamma receptors as regulators of immune responses. Nature Reviews. Immunology, 8, 34–47.

    PubMed  CAS  Google Scholar 

  33. Weiner, L. M., Dhodapkar, M. V., & Ferrone, S. (2009). Monoclonal antibodies for cancer immunotherapy. Lancet, 373, 1033–1040.

    PubMed  CAS  Google Scholar 

  34. Greenwood, J., Clark, M., & Waldmann, H. (1993). Structural motifs involved in human IgG antibody effector functions. European Journal of Immunology, 23, 1098–1104.

    PubMed  CAS  Google Scholar 

  35. Reff, E., Carner, K., Chambers, K. S., Chinn, P. C., Leonard, J. E., Raab, R., et al. (1994). Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood, 83, 435–445.

    PubMed  CAS  Google Scholar 

  36. Cooley, S., Burns, L. J., Repka, T., & Miller, J. S. (1999). Natural killer cell cytotoxicity of breast cancer targets is enhanced by two distinct mechanisms of antibody-dependent cellular cytotoxicity against LFA-3 and HER2/neu. Experimental Hematology, 27, 1533–1541.

    PubMed  CAS  Google Scholar 

  37. Manches, O., Lui, G., Chaperot, L., Gressin, R., Molens, J. P., Jacob, M. C., et al. (2003). In vitro mechanisms of action of rituximab on primary non-Hodgkin lymphomas. Blood, 101, 949–954.

    PubMed  CAS  Google Scholar 

  38. Dall’Ozzo, S., Tartas, S., Paintaud, G., Cartron, G., Colombat, P., Bardos, P., et al. (2004). Rituximab-dependent cytotoxicity by natural killer cells: influence of FCGR3A polymorphism on the concentration-effect relationship. Cancer Research, 64, 4664–4669.

    PubMed  Google Scholar 

  39. de Romeuf, C., Dutertre, C. A., Le Garff-Tavernier, M., Fournier, N., Gaucher, C., Glacet, A., et al. (2008). Chronic lymphocytic leukaemia cells are efficiently killed by an anti-CD20 monoclonal antibody selected for improved engagement of FcgammaRIIIA/CD16. British Journal Haematology, 140, 635–643.

    Google Scholar 

  40. Mössner, E., Brünker, P., Moser, S., Püntener, U., Schmidt, C., Herter, S., et al. (2010). 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, 115, 4393–4402.

    PubMed  Google Scholar 

  41. Savina, A., & Amigorena, S. (2007). Phagocytosis and antigen presentation in dendritic cells. Immunological Reviews, 219, 143–156.

    PubMed  CAS  Google Scholar 

  42. Rock, K. L., Gamble, S., & Rothstein, L. (1990). Presentation of exogenous antigen with class I major histocompatibility complex molecules. Science, 249, 918–921.

    PubMed  CAS  Google Scholar 

  43. Hart, S. P., Dougherty, G. J., Haslett, C., & Dransfield, I. (1997). CD44 regulates phagocytosis of apoptotic neutrophil granulocytes, but not apoptotic lymphocytes, by human macrophages. Journal of Immunology, 159, 919–925.

    CAS  Google Scholar 

  44. Banchereau, J., & Steinman, R. M. (1998). Dendritic cells and the control of immunity. Nature, 392, 245–252.

    PubMed  CAS  Google Scholar 

  45. Heath, W. R., Belz, G. T., Behrens, G. M. N., Smith, C. M., Forehan, S. P., Parish, I. A., et al. (2004). Cross-presentation, dendritic cell subsets, and the generation of immunity to cellular antigens. Immunological Reviews, 199, 9–26.

    PubMed  CAS  Google Scholar 

  46. Hazenbos, W. L., Heijnen, I. A., Meyer, D., Hofhuis, F. M., de Lavalette CR, Renardel, Schmidt, R. E., et al. (1998). Murine IgG1 complexes trigger immune effector functions predominantly via Fc gamma RIII (CD16). Journal of Immunoly, 161, 3026–3032.

    CAS  Google Scholar 

  47. Meyer, D., Schiller, C., Westermann, J., Izui, S., Hazenbos, W. L., Verbeek, J. S., et al. (1998). FcgammaRIII (CD16)-deficient mice show IgG isotype-dependent protection to experimental autoimmune hemolytic anemia. Blood, 92, 3902–3997.

    Google Scholar 

  48. Wernersson, S., Karlsson, M. C., Dahlstrom, J., Mattsson, R., Verbeek, J. S., & Heyman, B. (1999). IgG-mediated enhancement of antibody responses is low in Fc receptor gamma chain-deficient mice and increased in Fc gamma RII-deficient mice. Journal of Immunology, 163, 618–622.

    CAS  Google Scholar 

  49. Uchida, J., Hamaguchi, Y., Oliver, J. A., Ravetch, J. V., Poe, J. C., Haas, K. M., et al. (2004). The innate mononuclear phagocyte network depletes B lymphocytes through Fc receptor-dependent mechanisms during anti-CD20 antibody immunotherapy. The Journal of Experimental Medicine, 199, 1659–1669.

    PubMed  CAS  Google Scholar 

  50. Minard-Colin, V., Xiu, Y., Poe, J. C., Horikawa, M., Magro, C. M., Hamaguchi, Y., et al. (2008). Lymphoma depletion during CD20 immunotherapy in mice is mediated by macrophage FcgammaRI, FcgammaRIII, and FcgammaRIV. Blood, 112, 1205–1213.

    PubMed  CAS  Google Scholar 

  51. Oflazoglu, E., Stone, I. J., Gordon, K. A., Grewal, I. S., van Rooijen, N., Law, C. L., et al. (2007). Macrophages contribute to the anti-tumor activity of the anti-CD30 antibody SGN-30. Blood, 110, 4370–4372.

    PubMed  CAS  Google Scholar 

  52. Oflazoglu, E., Stone, I. J., Brown, L., Gordon, K. A., van Rooijen, N., Jonas, M., et al. (2009). Macrophages and Fc-receptor interactions contribute to the anti-tumour activities of the anti-CD40 antibody SGN-40. British Journal of Cancer, 100, 113–117.

    PubMed  CAS  Google Scholar 

  53. Leidi, M., Gotti, E., Bologna, L., Miranda, E., Rimoldi, M., Sica, A., et al. (2009). M2 macrophages phagocytose rituximab- opsonized leukemic targets more efficiently than m1 cells in vitro. Journal of Immunology, 182, 4415–4422.

    CAS  Google Scholar 

  54. Beers, S. A., Chan, C. H. T., French, R. R., Cragg, M. S., & Glennie, M. J. (2010). CD20 as a target for therapeutic type I and II monoclonal antibodies. Seminars in Hematology, 47, 107–114.

    PubMed  CAS  Google Scholar 

  55. Shibata-Koyama, M., Iida, S., Misaka, H., Mori, K., Yano, K., Shitara, K., et al. (2009). Nonfucosylated rituximab potentiates human neutrophil phagocytosis through its high binding for FcgammaRIIIb and MHC class II expression on the phagocytotic neutrophils. Experimental Hematology, 37, 309–321.

    PubMed  CAS  Google Scholar 

  56. Jerne, N. K. (1974). Towards a network theory of the immune system. Annales d’Immunologie, 125, 373–389.

    CAS  Google Scholar 

  57. Wettendorff, M., Iliopoulos, D., Tempero, M., Kay, D., DeFreitas, E., Koprowski, H., et al. (1989). Idiotypic cascades in cancer patients treated with monoclonal antibody CO17-1A. Proceedings of the National Academy of Sciences of the United States of America, 86, 3787–3791.

    PubMed  CAS  Google Scholar 

  58. Losman, M. J., Hansen, H. J., Sharkey, R. M., Goldenberg, D. M., & Monestier, M. (1991). Human response against NP-4, a mouse antibody to carcinoembryonic antigen: human anti-idiotype antibodies mimic an epitope on the tumor antigen. Proceedings of the National Academy of Sciences of the United States of America, 88, 3421–3425.

    PubMed  CAS  Google Scholar 

  59. Saleh, M. N., Stapleton, J. D., Khazaeli, M. B., & LoBuglio, A. F. (1993). Generation of a human anti-idiotypic antibody that mimics the GD2 antigen. Journal of Immunology, 151, 3390–3398.

    CAS  Google Scholar 

  60. Schultes, B. C., Baum, R. P., Niesen, A., Noujaim, A. A., & Madiyalakan, R. (1998). Anti-idiotype induction therapy: anti-CA125 antibodies (Ab3) mediated tumor killing in patients treated with Ovarex mAb B43.13 (Ab1). Cancer Immunology, Immunotherapy, 46, 201–212.

    PubMed  CAS  Google Scholar 

  61. Bradt, B. M., DeNardo, S. J., Mirick, G. R., & DeNardo, G. L. (2003). Documentation of idiotypic cascade after Lym-1 radioimmunotherapy in a patient with non-Hodgkin’s lymphoma: basis for extended survival? Clinical Cancer Research, 9, 4007–4012.

    Google Scholar 

  62. Hilchey, S., Hyrien, O., Mosmann, T., Livingstone, A., Friedberg, J., Young, F., et al. (2009). Rituximab immunotherapy results in the induction of a lymphoma idiotype-specific T-cell response in patients with follicular lymphoma: support for a "vaccinal effect" of rituximab. Blood, 113, 3809–3812.

    PubMed  CAS  Google Scholar 

  63. Kwak, L. W., Campbell, M. J., Czerwinski, D. K., Hart, S., Miller, R. A., & Levy, R. (1992). Induction of immune responses in patients with B-cell lymphoma against the surface-immunoglobulin idiotype expressed by their tumors. The New England Journal of Medicine, 327, 1209–1215.

    PubMed  CAS  Google Scholar 

  64. Cheung, N. K., Guo, H. F., Heller, G., & Cheung, I. Y. (2000). Induction of Ab3 and Ab3′ antibody was associated with long-term survival after anti-GD2 antibody therapy of stage 4 neuroblastoma. Clinical Cancer Research, 6, 2653–2660.

    PubMed  CAS  Google Scholar 

  65. Fagerberg, J., Frödin, J. E., Wigzell, H., & Mellstedt, H. (1993). Induction of an immune network cascade in cancer patients treated with monoclonal antibodies (ab1). I. May induction of ab1-reactive T cells and anti-anti-idiotypic antibodies (ab3) lead to tumor regression after mAb therapy? Cancer Immunology, Immunotherapy, 37, 264–270.

    PubMed  CAS  Google Scholar 

  66. Fagerberg, J., Steinitz, M., Wigzell, H., Askelöf, P., & Mellstedt, H. (1995). Human anti-idiotypic antibodies induced a humoral and cellular immune response against a colorectal carcinoma-associated antigen in patients. Proceedings of the National Academy of Sciences of the United States of America, 92, 4773–4777.

    PubMed  CAS  Google Scholar 

  67. Mittelman, A., Chen, Z. J., Yang, H., Wong, G. Y., & Ferrone, S. (1992). Human high molecular weight melanoma- associated antigen (HMW-MAA) mimicry by mouse anti-idiotypic monoclonal antibody MK2-23: induction of humoral anti-HMW-MAA immunity and prolongation of survival in patients with stage IV melanoma. Proceedings of the National Academy of Sciences of the United States of America, 89, 466–470.

    PubMed  CAS  Google Scholar 

  68. Foon, K. A., Sen, G., Hutchins, L., Kashala, O. L., Baral, R., Banerjee, M., et al. (1998). Antibody responses in melanoma patients immunized with an anti-idiotype antibody mimicking disialoganglioside GD2. Clinical Cancer Research, 4, 1117–1124.

    PubMed  CAS  Google Scholar 

  69. Yao, T. J., Meyers, M., Livingston, P. O., Houghton, A. N., & Chapman, P. B. (1999). Immunization of melanoma patients with BEC2-keyhole limpet hemocyanin plus BCG intradermally followed by intravenous booster immunizations with BEC2 to induce anti-GD3 ganglioside antibodies. Clinical Cancer Research, 5, 77–81.

    PubMed  CAS  Google Scholar 

  70. Durrant, L. G., Parsons, T., Moss, R., Spendlove, I., Carter, G., & Carr, F. (2001). Human anti-idiotypic antibodies can be good immunogens as they target Fc receptors on antigen-presenting cells allowing efficient stimulation of both helper and cytotoxic T-cell responses. International Journal of Cancer, 92, 414–420.

    CAS  Google Scholar 

  71. Wagner, U., Köhler, S., Reinartz, S., Giffels, P., Huober, J., Renke, K., et al. (2001). Immunological consolidation of ovarian carcinoma recurrences with monoclonal anti-idiotype antibody ACA125: immune responses and survival in palliative treatment. See The biology behind: K. A. Foon and M. Bhattacharya-Chatterjee, Are solid tumor anti-idiotype vaccines ready for prime time? Clinical Cancer Research, 7, 1112–1115. Clin Cancer Res 7: 1154-1162, 2001.

    Google Scholar 

  72. Murray, J. L., Gillogly, M., Kawano, K., Efferson, C. L., Lee, J. E., Ross, M., et al. (2004). Fine specificity of high molecular weight-melanoma-associated antigen-specific cytotoxic T lymphocytes elicited by anti- idiotypic monoclonal antibodies in patients with melanoma. Cancer Research, 64, 5481–5488.

    PubMed  CAS  Google Scholar 

  73. Köhler, G., & Milstein, C. (1975). Continuous cultures of fused cells secreting antibodies of predefined specificity. Nature, 256, 495–497.

    PubMed  Google Scholar 

  74. Cartron, G., Watier, H., Golay, J., & Solal-Celigny, P. (2004). From the bench to the bedside: ways to improve rituximab efficacy. Blood, 104, 2635–2642.

    PubMed  CAS  Google Scholar 

  75. Lim, S., Beers, S., French, R., Johnson, P., Glennie, M., & Cragg, M. (2010). Anti-CD20 monoclonal antibodies—historical and future perspectives. Haematologica, 115, 5191–5201.

    Google Scholar 

  76. Abès, R., Gélizé, E., Fridman, W. H., & Teillaud, J. L. (2010). Long-lasting antitumor protection by anti-CD20 antibody through cellular immune response. Blood, 116, 926–934.

    PubMed  Google Scholar 

  77. Weiner, L. M., Surana, R., & Wang, S. (2010). Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nature Revue d’Immunologie, 10, 317–327.

    CAS  Google Scholar 

  78. Dhodapkar, K. M., & Dhodapkar, M. V. (2005). Recruiting dendritic cells to improve antibody therapy of cancer. Proceedings of the National Academy of Sciences of the United States of America, 102, 6243–6244.

    PubMed  CAS  Google Scholar 

  79. Sala, A., Gresser, I., Chassoux, D., Maury, C., Santodonato, L., Eid, P., et al. (1992). Inhibition of Friend leukemia cell visceral metastases by a new monoclonal antibody and role of the immune system of the host in its action. Cancer Research, 52, 2880–2890.

    PubMed  CAS  Google Scholar 

  80. Linehan, D. C., Goedegebuure, P. S., Peoples, G. E., Rogers, S. O., & Eberlein, T. J. (1995). Tumor-specific and HLA-A2- restricted cytolysis by tumor-associated lymphocytes in human metastatic breast cancer. Journal of Immunology, 155, 4486–4491.

    CAS  Google Scholar 

  81. Peoples, G. E., Goedegebuure, P. S., Smith, R., Linehan, D. C., Yoshino, I., & Eberlein, T. J. (1995). Breast and ovarian cancer-specific cytotoxic T lymphocytes recognize the same HER2/neu-derived peptide. Proceedings of the National Academy of Sciences of the United States of America, 92, 432–435.

    PubMed  CAS  Google Scholar 

  82. Kawashima, I., Hudson, S. J., Tsai, V., Southwood, S., Takesako, K., Appella, E., et al. (1998). The multi-epitope approach for immunotherapy for cancer: identification of several CTL epitopes from various tumor-associated antigens expressed on solid epithelial tumors. Human Immunology, 59, 1–14.

    PubMed  CAS  Google Scholar 

  83. Rongcun, Y., Salazar-Onfray, F., Charo, J., Malmberg, K. J., Evrin, K., Maes, H., et al. (1999). Identification of new HER2/neu-derived peptide epitopes that can elicit specific CTL against autologous and allogeneic carcinomas and melanomas. Journal of Immunology, 163, 1037–1044.

    CAS  Google Scholar 

  84. Sotiriadou, R., Perez, S. A., Gritzapis, A. D., Sotiropoulou, P. A., Echner, H., Heinzel, S., et al. (2001). Peptide HER2(776-788) represents a naturally processed broad MHC class II-restricted T cell epitope. British Journal of Cancer, 85, 1527–1534.

    PubMed  CAS  Google Scholar 

  85. Gritzapis, A. D., Voutsas, I. F., Lekka, E., Tsavaris, N., Missitzis, I., Sotiropoulou, P., et al. (2008). Identification of a novel immunogenic HLA-A*0201-binding epitope of HER-2/neu with potent antitumor properties. Journal of Immunology, 181, 146–154.

    CAS  Google Scholar 

  86. Ikuta, Y., Okugawa, T., Furugen, R., Nagata, Y., Takahashi, Y., Wang, L., et al. (2000). A HER2/NEU-derived peptide, a Kd-restricted murine tumor rejection antigen, induces HER2-specific HLA-A2402-restricted CD8+ cytotoxic T lymphocytes. International Journal of Cancer, 87, 553–558.

    CAS  Google Scholar 

  87. Gritzapis, A. D., Mahaira, L. G., Perez, S. A., Cacoullos, N. T., Papamichail, M., & Baxevanis, C. N. (2006). Vaccination with human HER- 2/neu (435-443) CTL peptide induces effective antitumor immunity against HER-2/neu-expressing tumor cells in vivo. Cancer Research, 66, 5452–5460.

    PubMed  CAS  Google Scholar 

  88. Voutsas, I. F., Gritzapis, A. D., Mahaira, L. G., Salagianni, M., von Hofe, E., Kallinteris, N. L., et al. (2007). Induction of potent CD4+ T cell-mediated antitumor responses by a helper HER-2/neu peptide linked to the Ii-Key moiety of the invariant chain. International Journal of Cancer, 121, 2031–2041.

    CAS  Google Scholar 

  89. Li, S., Yang, J., Urban, F. A., Macgregor, J. N., Hughes, D. P. M., Chang, A. E., et al. (2008). Genetically engineered T cells expressing a HER2-specific chimeric receptor mediate antigen-specific tumor regression. Cancer Gene Therapy, 15, 382–392.

    PubMed  CAS  Google Scholar 

  90. Kim, P. S., Armstrong, T. D., Song, H., Wolpoe, M. E., Weiss, V., Manning, E. A., et al. (2008). Antibody association with HER-2/neu-targeted vaccine enhances CD8 T cell responses in mice through Fc-mediated activation of DCs. Journal of Clinical Investigation, 118, 1700–1711.

    PubMed  CAS  Google Scholar 

  91. Clemenceau, B., Vivien, R., Berthomé, M., Robillard, N., Garand, N., Gallot, G., et al. (2008). Effector memory alphabeta T lymphocytes can express Fcgamma RIIIa and mediate antibody-dependent cellular cytotoxicity. Journal of Immunology, 180, 5327–5334.

    CAS  Google Scholar 

  92. Bargou, R., Leo, E., Zugmaier, G., Klinger, M., Goebeler, M., Knop, S., et al. (2008). Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science, 321, 974–977.

    PubMed  CAS  Google Scholar 

  93. de Bono, J. S., Rha, S. Y., Stephenson, J., Schultes, B. C., Monroe, P., Eckhardt, G. S., et al. (2004). Phase I trial of a murine antibody to MUC1 in patients with metastatic cancer: evidence for the activation of humoral and cellular antitumor immunity. Annals of Oncology, 15, 1825–1833.

    PubMed  Google Scholar 

  94. Taylor, C., Hershman, D., Shah, N., Suciu-Foca, N., Petrylak, D. P., Taub, R., et al. (2007). Augmented HER-2 specific immunity during treatment with trastuzumab and chemotherapy. Clinical Cancer Research, 13, 5133–5143.

    PubMed  CAS  Google Scholar 

  95. Selenko, N., Maidic, O., Draxier, S., Berer, A., Jäger, U., Knapp, W., et al. (2001). CD20 antibody (C2B8)-induced apoptosis of lymphoma cells promotes phagocytosis by dendritic cells and cross-priming of CD8+ cytotoxic T cells. Leukemia, 15, 1619–1626.

    PubMed  CAS  Google Scholar 

  96. Selenko, N., Majdic, O., Jäger, U., Sillaber, C., Stöckl, J., & Knapp, W. (2002). Cross-priming of cytotoxic T cells promoted by apoptosis-inducing tumor cell reactive antibodies? Journal of Clinical Immunology, 22, 124–130.

    PubMed  CAS  Google Scholar 

  97. Gadri, Z., Kukulansky, T., Bar-Or, E., Haimovich, J., & Hollander, N. (2009). Synergistic effect of dendritic cell vaccination and anti-CD20 antibody treatment in the therapy of murine lymphoma. Journal of Immunotherapy, 32, 333–340.

    PubMed  CAS  Google Scholar 

  98. Davis, T. A., Grillo-López, A. J., White, C. A., McLaughlin, P., Czuczman, M. S., Link, B. K., et al. (2000). Rituximab anti-CD20 monoclonal antibody therapy in non-Hodgkin’s lymphoma: safety and efficacy of re-treatment. 3143, 18, 3135–3143.

    CAS  Google Scholar 

  99. Hainsworth, J. D., Litchy, S., Burris, H. A., Scullin, D. C., Corso, S. W., Yardley, D. A., et al. (2002). Rituximab as first-line and maintenance therapy for patients with indolent non-Hodgkin’s lymphoma. Journal of Clinical Oncology, 20, 4261–4267.

    PubMed  CAS  Google Scholar 

  100. Weng, W. K., Czerwinski, D., & Levy, R. (2007). Humoral immune response and immunoglobulin G Fc receptor genotype are associated with better clinical outcome following idiotype vaccination in follicular lymphoma patients regardless of their response to induction chemotherapy. Blood, 109, 951–953.

    PubMed  CAS  Google Scholar 

  101. Bohen, S. P., Troyanskaya, O. G., Alter, O., Warnke, R., Botstein, D., Brown, P. O., et al. (2003). Variation in gene expression patterns in follicular lymphoma and the response to rituximab. Proceedings of the National Academy of Sciences of the United States of America, 100, 1926–1930.

    PubMed  CAS  Google Scholar 

  102. Jais, J. P., Haioun, C., Molina, T. J., Rickman, D. S., de Reynies, A., Berger, F., et al. (2008). Groupe d’Etude des Lymphomes de l’Adulte: the expression of 16 genes related to the cell of origin and immune response predicts survival in elderly patients with diffuse large B-cell lymphoma treated with CHOP and rituximab. Leukemia, 22, 1917–1924.

    PubMed  CAS  Google Scholar 

  103. di Gaetano, N., Cittera, E., Nota, R., Vecchi, A., Grieco, V., Scanziani, E., et al. (2003). Complement activation determines the therapeutic activity of rituximab in vivo. Journal of Immunology, 171, 1581–1587.

    Google Scholar 

  104. Corthay, A., Skovseth, D. K., Lundin, K. U., Røsjø, E., Omholt, H., Hofgaard, P. O., et al. (2005). Primary antitumor immune response mediated by CD4+ T cells. Immunity, 22, 371–383.

    PubMed  CAS  Google Scholar 

  105. Perez-Diez, A., Joncker, N. T., Choi, K., Chan, W. F. N., Anderson, C. C., Lantz, O., et al. (2007). CD4 cells can be more efficient at tumor rejection than CD8 cells. Blood, 109, 5346–5354.

    PubMed  CAS  Google Scholar 

  106. Khalil, M., & Vonderheide, R. H. (2007). Anti-CD40 agonist antibodies: preclinical and clinical experience. Update on Cancer Therapeutics, 2, 61–65.

    PubMed  Google Scholar 

  107. Advani, R., Forero-Torres, A., Furman, R. R., Rosenblatt, J. D., Younes, A., Ren, H., et al. (2007). Phase I study of the humanized anti-CD40 monoclonal antibody dacetuzumab in refractory or recurrent non-Hodgkin’s lymphoma. Journal of Clinical Oncology, 27, 4371–4377.

    Google Scholar 

  108. Sarnaik, A. A., & Weber, J. S. (2009). Recent advances using anti-CTLA-4 for the treatment of melanoma. Cancer Journal, 15, 169–173.

    CAS  Google Scholar 

  109. Gough, M. J., Ruby, C. E., Redmond, W. L., Dhungel, B., Brown, A., & Weinberg, A. D. (2008). OX40 agonist therapy enhances CD8 infiltration and decreases immune suppression in the tumor. Cancer Research, 68, 5206–5215.

    PubMed  CAS  Google Scholar 

  110. Berger, R., Rotem-Yehudar, R., Slama, G., Landes, S., Kneller, A., Leiba, M., et al. (2008). Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies. Clinical Cancer Research, 14, 3044–3051.

    PubMed  CAS  Google Scholar 

  111. Coiffier, B., Lepage, E., Briere, J., Herbrecht, R., Tilly, H., Bouabdallah, R., et al. (2002). CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. The New England Journal of Medicine, 346, 235–242.

    PubMed  CAS  Google Scholar 

  112. Forstpointner, R., Dreyling, M., Repp, R., Hermann, S., Hänel, A., Metzner, B., et al. (2004). German Low-Grade Lymphoma Study Group: 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, 104, 3064–3071.

    PubMed  CAS  Google Scholar 

  113. Coiffier, B., Thieblemont, C., van Den Neste, E., Lepeu, G., Plantier, I., Castaigne, S., et al. (2010). Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood, 116, 2040–2045.

    PubMed  CAS  Google Scholar 

  114. Bonner, J. A., Harari, P. M., Giralt, J., Cohen, R. B., Jones, C. U., Sur, R. K., et al. (2010). Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. The Lancet Oncology, 11, 21–28.

    PubMed  CAS  Google Scholar 

  115. Willett, C. G., Duda, D. G., di Tomaso, E., Boucher, Y., Ancukiewicz, M., Sahani, D. V., et al. (2009). Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study. Journal of Clinical Oncology, 27, 3020–3026.

    PubMed  CAS  Google Scholar 

  116. Gulley, J. L., Arlen, P. M., Bastian, A., Morin, S., Marte, J., Beetham, P., et al. (2005). Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer. Clinical Cancer Research, 11, 3353–3362.

    PubMed  CAS  Google Scholar 

  117. Roses, R. E., Xu, M., Koski, G. K., & Czerniecki, B. J. (2008). Radiation therapy and Toll-like receptor signaling: implications for the treatment of cancer. Oncogene, 27, 200–207.

    PubMed  CAS  Google Scholar 

  118. Zitvogel, L., & Kroemer, G. (2009). Anticancer immunochemotherapy using adjuvants with direct cytotoxic effects. Journal of Clinical Investigation, 119, 2127–2130.

    PubMed  CAS  Google Scholar 

  119. Kimby, E., Jurlander, J., Geisler, C., Hagberg, H., Holte, H., Lehtinen, T., et al. (2008). Nordic Lymphoma Group: long-term molecular remissions in patients with indolent lymphoma treated with rituximab as a single agent or in combination with interferon alpha-2a: a randomized phase II study from the Nordic Lymphoma Group. Leukemia & Lymphoma, 49, 102–112.

    CAS  Google Scholar 

  120. Cartron, G., Zhao-Yang, L., Baudard, M., Kanouni, T., Rouillé, V., Quittet, P., et al. (2008). Granulocyte-macrophage colony- stimulating factor potentiates rituximab in patients with relapsed follicular lymphoma: results of a phase II study. Journal of Clinical Oncology, 26, 2725–2731.

    PubMed  CAS  Google Scholar 

  121. Khan, K. D., Emmanouilides, C., Benson, D. M., Hurst, D., Garcia, P., Michelson, G., et al. (2006). A phase 2 study of rituximab in combination with recombinant interleukin-2 for rituximab-refractory indolent non-Hodgkin’s lymphoma. Clinical Cancer Research, 12, 7046–7053.

    PubMed  CAS  Google Scholar 

  122. Overwijk, W. W., Theoret, M. R., & Restifo, N. P. (2000). The future of interleukin-2: enhancing therapeutic anticancer vaccines. The Cancer Journal from Scientific American, 6, 576–580.

    Google Scholar 

  123. Brandenburg, S., Takahashi, T., de la Rosa, M., Janke, M., Karsten, G., Muzzulini, T., et al. (2008). IL-2 induces in vivo suppression by CD4+ CD25+ Foxp3+ regulatory T cells. European Journal of Immunology, 38, 1643–1653.

    PubMed  CAS  Google Scholar 

  124. Park, S. G., Jiang, Z., Mortenson, E. D., Deng, L., Radkevich-Brown, O., Yang, X., et al. (2010). The therapeutic effect of anti-HER2/neu antibody depends on both innate and adaptive immunity. Cancer Cell, 18, 160–170.

    Google Scholar 

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Acknowledgments

This work was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), the University René Descartes-Paris 5, the University Pierre et Marie Curie (UPMC)-Paris 6, and the Laboratoire français du Fractionnement et des Biotechnologies (LFB). Riad Abès was previously supported by the Laboratoire français du Fractionnement et des Biotechnologies (LFB) and the Association Nationale de la Recherche et de la Technologie (ANRT) (CIFRE fellowship #173/2006).

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The authors declare that they have no competing financial interests.

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Abès, R., Teillaud, JL. Modulation of tumor immunity by therapeutic monoclonal antibodies. Cancer Metastasis Rev 30, 111–124 (2011). https://doi.org/10.1007/s10555-011-9282-3

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