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Antibody Therapy for Non-Hodgkin’s Lymphoma

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Immunotherapy of Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Monoclonal antibodies have made a significant impact on the treatment of non-Hodgkin’s lymphoma (NHL), and there has been a dramatic increase in clinical data regarding their use. The anti-CD20 antibody, rituximab, has shown substantial single-agent activity in both indolent and aggressive B-cell lymphomas. Rituximab is now standard therapy in relapsed indolent NHL, and it is the front-line treatment in combination with cyclophosphamide/doxorubicin/vincristine/prednisone chemotherapy for patients with large B-cell lymphoma. Combinations of rituximab with other cytotoxic agents or cytokines are currently being explored in a number of different studies, and some of these combinations show promise for the future. Other antibodies directed at different targets on lymphoma cells, such as epratuzumab, apolizumab, alemtuzumab, and galiximab, have also shown clinical activity in early trials. The radioconjugated anti-CD20 antibodies 90yttrium ibritumomab tiuxetan and 131iodine tositumomab also have significant clinical activity in low-grade B-cell NHL, and the former has demonstrated superior complete response rates when compared with rituximab. The challenge for the future will be to determine the place of each antibody in the treatment of NHL.

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References

  1. Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer statistics, 2001. CA Cancer J Clin 2001; 51:15–36.

    PubMed  CAS  Google Scholar 

  2. Valentine MA, Meier KE, Rossie S, Clark EA. Phosphorylation of the CD20 phosphoprotein in resting Blymphocytes. J Biol Chem 1989; 264:11,282–11,287.

    PubMed  CAS  Google Scholar 

  3. Einfeld DA, Brown JP, Valentine MA, Clark EA, Ledbetter JA. Molecular cloning of the human B cell CD20 receptor predicts a hydrophobic protein with multiple transmembrane domains. EMBO J 1988; 7:711–717.

    PubMed  CAS  Google Scholar 

  4. 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.

    PubMed  CAS  Google Scholar 

  5. Anderson KC, Bates MP, Slaughenhoupt B, Schlossman SF, Nadler LM. Expression of human B cellassociated antigens on leukemias and lymphomas: A model of human B cell differentiation. Blood 1984; 63:1424–1433.

    PubMed  CAS  Google Scholar 

  6. Tedder TF, Boyd AW, Freedman AS, Nadler LM, Schlossman SFl. The B cell surface molecule B1 is functionally linked with B cell activation and differentiation. J Immunol 1985; 135:973–979.

    PubMed  CAS  Google Scholar 

  7. Shan D, Ledbetter JA, Press OW. Signaling events involved in anti-CD20-induced apoptosis of malignant human B cells. Cancer Immunol Immunother 2000; 48:673–683.

    Article  PubMed  CAS  Google Scholar 

  8. Hofmeister JK, Cooney D, Coggeshall KM. Clustered CD20 induced apoptosis: Src-family kinase, the proximal regulator of tyrosine phosphorylation calcium influx and caspase 3-dependent apoptosis. Blood Cell Mol Dis 2000; 26:133–143.

    Article  CAS  Google Scholar 

  9. Golay J, Zaffaroni L, Vaccari T, et al. Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis. Blood 2000; 95:3900–3908.

    PubMed  CAS  Google Scholar 

  10. Harjunpaa A, Junnikkala S, Meri S. Rituximab (anti-CD20) therapy of B cell lymphomas: direct complement killing is superior to cellular effector mechanisms. Scand J Immunol 2000; 51:634–641.

    Article  PubMed  CAS  Google Scholar 

  11. Wurflein D, Dechant M, Stockmeyer B, et al. Evaluating antibodies for their capacity to induce cell-mediated lysis of malignant B cells. Cancer Res 1998; 58:3051–3058.

    PubMed  CAS  Google Scholar 

  12. Elsasser D, Valerius T, Repp R, et al. HLA class II as potential target antigen on malignant B cells for therapy with bispecific antibodies in combination with granulocyte colony-stimulating factor. Blood 1996; 87:3803–3812.

    PubMed  CAS  Google Scholar 

  13. Uchida J, Hamaguchi Y, Oliver JA, et al. The innate mononuclear phagocyte network depletes B lymphocytes through Fc receptor-dependent mechanisms during anti-CD20 antibody immunotherapy. J Exp Med 2004; 199:1659–1669.

    Article  PubMed  CAS  Google Scholar 

  14. Hernandez-Ilizaliturri FJ, Jupudy V, Ostberg J, et al. Neutrophils contribute to the biological antitumor activity of rituximab in a non-Hodgkin’s lymphoma severe combined immunodeficiency mouse model. Clin Cancer Res 2003; 9(Pt 1):5866–5873.

    PubMed  CAS  Google Scholar 

  15. Golay JT, Clark EA, Beverley PC. The CD20 (Bp35) antigen is involved in activation of B cells from the G0 to the G1 phase of the cell cycle. J Immunol 1985; 135:3795–3801.

    PubMed  CAS  Google Scholar 

  16. Bubien JK, Zhou LJ, Bell PD, Frizzell RA, Tedder TF. Transfection of the CD20 cell surface molecule into ectopic cell types generates a Ca2+ conductance found constitutively in B lymphocytes. J Cell Biol 1993; 121:1121–1132.

    Article  PubMed  CAS  Google Scholar 

  17. Pedersen IM, Buhl AM, Klausen P, Geisler CH, Jurlander J. The chimeric anti-CD20 antibody rituximab induces apoptosis in B-cell chronic lymphocytic leukemia cells through a p38 mitogen activated proteinkinase-dependent mechanism. Blood 2002; 99:1314–1319.

    Article  PubMed  CAS  Google Scholar 

  18. Byrd JC, Kitada S, Flinn IW, 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; 99:1038–1043.

    Article  PubMed  CAS  Google Scholar 

  19. Alas S, Ng CP, Bonavida B. Rituximab modifies the cisplatin-mitochondrial signaling pathway, resulting in apoptosis in cisplatin-resistant non-Hodgkin’s lymphoma. Clin Cancer Res 2002; 8:836–845.

    PubMed  CAS  Google Scholar 

  20. Deans JP, Li H, Polyak MJ. CD20-mediated apoptosis: signalling through lipid rafts. Immunology 2002; 107:176–182.

    Article  PubMed  CAS  Google Scholar 

  21. Petrie RJ, Deans JP. Colocalization of the B cell receptor and CD20 followed by activation-dependent dissociation in distinct lipid rafts. J Immunol 2002; 169:2886–2891.

    PubMed  CAS  Google Scholar 

  22. van Ojik HH, Bevaart L, Dahle CE, et al. CpG-A and B oligodeoxynucleotides enhance the efficacy of antibody therapy by activating different effector cell populations. Cancer Res 2003; 63:5595–5600.

    PubMed  Google Scholar 

  23. Clynes RA, Towers TL, Presta LG, Ravetch JV. Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Nat Med 2000; 6:443–446.

    Article  PubMed  CAS  Google Scholar 

  24. 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.

    Article  PubMed  CAS  Google Scholar 

  25. Cragg MS, Morgan SM, Chan HT, et al. Complement-mediated lysis by anti-CD20 mAb correlates with segregation into lipid rafts. Blood 2003; 101:1045–1052.

    Article  PubMed  CAS  Google Scholar 

  26. Di Gaetano N, Cittera E, Nota R, et al. Complement activation determines the therapeutic activity of rituximab in vivo. J Immunol 2003; 171:1581–1587.

    PubMed  Google Scholar 

  27. 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’s lymphoma. Blood 2001; 98:1352–1357.

    Article  PubMed  CAS  Google Scholar 

  28. Maloney DG, Grillo-Lopez AJ, White CA, et al. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy patients with relapsed low-grade non-Hodgkin’s lymphoma. Blood 1997; 90:2188–2195.

    PubMed  CAS  Google Scholar 

  29. Maloney DG, Grillo-Lopez AJ, Bodkin DJ, et al. IDEC-C2B8: results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin’s lymphoma. J Clin Oncol 1997; 15:3266–3274.

    PubMed  CAS  Google Scholar 

  30. 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.

    PubMed  CAS  Google Scholar 

  31. Colombat P, Salles G, Brousse N, 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; 97:101–106.

    Article  PubMed  CAS  Google Scholar 

  32. Hainsworth JD, Litchy S, Burris HA III, et al. Rituximab as first-line and maintenance therapy for patients with indolent non-hodgkin’s lymphoma. J Clin Oncol 2002; 20:4261–4267.

    Article  PubMed  CAS  Google Scholar 

  33. Witzig TE, Vukov AM, Habermann TM, et al. Rituximab therapy for patients with newly diagnosed, advanced-stage follicular grade I non-Hodgkin’s lymphoma: a Phase II trial in the North Central Cancer Treatment Group. J Clin Oncol 2005; 23:1056–1058.

    Article  Google Scholar 

  34. Hainsworth JD. First-line and maintenance treatment with rituximab for patients with indolent non-Hodgkin’s lymphoma. Semin Oncol 2003; 30(Suppl 2):9–15.

    Article  PubMed  CAS  Google Scholar 

  35. Piro LD, White CA, Grillo-Lopez AJ, et al. Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin’s lymphoma. Ann Oncol 1999; 10:655–661.

    Article  PubMed  CAS  Google Scholar 

  36. Ghielmini M, Schmitz SF, Cogliatti SB, 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; 103:4416–4423.

    Article  PubMed  CAS  Google Scholar 

  37. Czuczman MS, Grillo-Lopez AJ, White CA, et al. Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol 1999; 17:268–276.

    PubMed  CAS  Google Scholar 

  38. Vose JM, Link BK, Grossbard ML, et al. Phase II study of rituximab in combination with chop chemotherapy in patients with previously untreated, aggressive non-Hodgkin’s lymphoma. J Clin Oncol 2001; 19:389–397.

    PubMed  CAS  Google Scholar 

  39. Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 2002; 346:235–242.

    Article  PubMed  CAS  Google Scholar 

  40. Habermann TM, Weller EA, Morrison VA, et al. Phase III trial of rituximab-CHOP (R-CHOP) vs. CHOP with a second randomization to maintenance rituximab (MR) or observation in patients 60 years of age and older with diffuse large B-cell lymphoma (DLBCL). Blood 2003; 102:248 (abstract no. 870).

    Google Scholar 

  41. Davis TA, Maloney DG, Czerwinski DK, Liles TM, Levy R. Anti-idiotype antibodies can induce longterm complete remissions in non-Hodgkin’s lymphoma without eradicating the malignant clone. Blood 1998; 92:1184–1190.

    PubMed  CAS  Google Scholar 

  42. Sacchi S, Federico M, Vitolo U, et al. GISL. Clinical activity and safety of combination immunotherapy with IFN-alpha 2a and Rituximab in patients with relapsed low grade non-Hodgkin’s lymphoma. Haematologica 2001; 86:951–958.

    PubMed  CAS  Google Scholar 

  43. 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.

    Article  PubMed  CAS  Google Scholar 

  44. 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.

    Article  PubMed  CAS  Google Scholar 

  45. Jahrsdorfer B, Weiner GJ. Immunostimulatory CpG oligodeoxynucleotides and antibody therapy of cancer. Semin Oncol 2003; 30:476–482.

    Article  PubMed  CAS  Google Scholar 

  46. Jahrsdorfer B, Hartmann G, Racila E, et al. CpG DNA increases primary malignant B cell expression of costimulatory molecules and target antigens. J Leukoc Biol 2001; 69:81–88.

    PubMed  CAS  Google Scholar 

  47. Leung SO, Goldenberg DM, Dion AS, et al. Construction and characterization of a humanized, internalizing, B-cell (CD22)-specific, leukemia/lymphoma antibody, LL2. Mol Immunol 1995; 32:1413–1427.

    Article  PubMed  CAS  Google Scholar 

  48. Leonard JP, Coleman M, Ketas JC, et al. Phase I/II trial of epratuzumab (humanized anti-CD22 antibody) in indolent non-Hodgkin’s lymphoma. J Clin Oncol 2003; 21(16):3051–3059.

    Article  PubMed  CAS  Google Scholar 

  49. Leonard JP, Coleman M, Matthews JC, et al. Epratuzumab (Anti-CD22) and rituximab (anti-CD20) combination immunotherapy for non-Hodgkin’s lymphoma: preliminary response data. Proc Am Soc Clin Oncol 2002; 21:1060a.

    Google Scholar 

  50. Coleman M, Goldenberg DM, Siegel AB, et al. Epratuzumab: targeting B-cell malignancies through CD22. Clin Cancer Res 2003; 9:39,915–39,945.

    Google Scholar 

  51. Micallef INM, Kahl B, Gayko U, et al. A pilot study of epratuzumab and rituximab in combination with CHOP chemotherapy (ER-CHOP) in previously untreated patients with diffuse large B-cell lymphoma (DLBCL). Proc Am Soc Hematol 2003.

    Google Scholar 

  52. Bains SK, Mone A, Yun Tso J, et al. Mitochondria control of cell death induced by anti-HLA-DR antibodies. Leukemia 2003; 17:1357–1365.

    Article  PubMed  CAS  Google Scholar 

  53. Link BK, Wang H, Byrd JC, et al. Phase I study of Hu1D10 monoclonal antibody in patients with B-cell lymphoma. Proc Am Soc Clin Oncol 2001; 20:284a.

    Google Scholar 

  54. Link BK, Wang H, Byrd JC, et al. Prolonged clinical responses in patients with follicular lymphoma treated on a Phase I trial of the anti-hla-dr monoclonal antibody Remitogena (Hu1D10). Proc Am Soc Hematol 2001; 98:244b.

    Google Scholar 

  55. Link BK, Kahl B, Czuczman M, et al. A Phase II study of Remitogen™; (Hu1D10), a humanized monoclonal antibody in patients with relapsed or refractory follicular, small lymphocytic, or marginal zone/MALT B-cell lymphoma. Proc Am Soc Hematol 2001; 98:2540.

    Google Scholar 

  56. Lundin J, Osterborg A, Brittinger G, et al. CAMPATH-1H monoclonal antibody in therapy for previously treated low-grade non-Hodgkin’s lymphomas: a phase II multicenter study. European Study Group of CAMPATH-1H treatment in low-grade non-Hodgkin’s lymphoma. J Clin Oncol 1998; 16:3257–3263.

    PubMed  CAS  Google Scholar 

  57. Khorana A, Bunn P, McLaughlin P, Vose J, Stewart C, Czuczman MS. A phase II multicenter study of CAMPATH-1H antibody in previously treated patients with nonbulky non-Hodgkin’s lymphoma. Leuk Lymphoma 2001; 41:77–87.

    Article  PubMed  CAS  Google Scholar 

  58. 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 2003; 3:257–259.

    Article  PubMed  CAS  Google Scholar 

  59. Ansell S, Byrd J, Horwitz S, et al. Phase I/II study of a fully human anti-CD30 monoclonal antibody (MDX-060) in Hodgkin’s disease (HD) and anaplastic large cell lymphoma (ALCL). Blood 2003; 102:181a.

    Google Scholar 

  60. Bartlett NL, Bernstein SH, Leonard JP, et al. Safety, antitumor activity and pharmacokinetics of six weekly doses of SGN-30 (anti-CD30 monoclonal antibody) in patients with refractory or recurrent CD30+ hematologic malignancies. Blood 2003; 102:647a.

    Google Scholar 

  61. Kaminski MS, Zasadny KR, Francis IR, et al. Iodine-131-anti-B1 radioimmunotherapy for B-cell lymphoma. J Clin Oncol 1996; 14:1974–1981.

    PubMed  CAS  Google Scholar 

  62. Liu SY, Eary JF, Petersdorf SH, et al. Follow-up of relapsed B-cell lymphoma patients treated with iodine-131-labeled anti-CD20 antibody and autologous stem-cell rescue. J Clin Oncol 1998; 16:3270–3278.

    PubMed  CAS  Google Scholar 

  63. Witzig TE, White CA, Wiseman GA, et al. Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20(+) B-cell non-Hodgkin’s lymphoma. J Clin Oncol 1999; 17:3793–3803.

    PubMed  CAS  Google Scholar 

  64. Witzig TE, White CA, Gordon LI, et al. Safety of yttrium-90 ibritumomab tiuxetan radioimmunotherapy for relapsed low-grade, follicular, or transformed non-Hodgkin’s lymphoma. J Clin Oncol 2003; 21:1263–1270.

    Article  PubMed  CAS  Google Scholar 

  65. Witzig TE, Gordon LI, Cabanillas F, 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; 20:2453–2463.

    Article  PubMed  CAS  Google Scholar 

  66. Press OW, Unger JM, Braziel RM, et al. A phase 2 trial of CHOP chemotherapy followed by tositumomab/iodine I 131 tositumomab for previously untreated follicular non-Hodgkin’s lymphoma: Southwest Oncology Group Protocol S9911. Blood 2003; 102:1606–1612.

    Article  PubMed  CAS  Google Scholar 

  67. Vose JM, Colcher D, Gobar L, et al. Phase I/II trial of multiple dose 131Iodine-MAb LL2 (CD22) in patients with recurrent non-Hodgkin’s lymphoma. Leuk Lymphoma 2000; 3:91–101.

    Google Scholar 

  68. Denardo GL, Lamborn KR, Goldstein DS, Kroger LA, Denardo SJ. Increased survival associated with radiolabeled Lym-1 therapy for non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. Cancer 1997; 80:2706–2711.

    Article  PubMed  CAS  Google Scholar 

  69. Postema EJ, Raemaekers JM, Oyen WJ, et al. Final results of a phase I radioimmunotherapy trial using (186)Re-epratuzumab for the treatment of patients with non-Hodgkin’s lymphoma. Clin Cancer Res 2003; 9(10 Pt 2):3995S–4002S.

    PubMed  CAS  Google Scholar 

  70. Schilder RJ, Witzig TE, Gordon L, et al. 90Y ibritumomab tiuxetan (Zevalin¨) radioimmunotherapy does not preclude effective delivery of subsequent therapy for lymphoma. Proc Am Soc Clin Oncol 2002; 21:267a.

    Google Scholar 

  71. Ansell SM, Ristow KM, Habermann TM, Wiseman GA, Witzig TE. Subsequent chemotherapy regimens are well tolerated after radioimmunotherapy with yttrium-90 ibritumomab tiuxetan for non-Hodgkin’s lymphoma. J Clin Oncol 2002; 20:3885–3890.

    Article  PubMed  CAS  Google Scholar 

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Ansell, S.M., Witzig, T.E. (2006). Antibody Therapy for Non-Hodgkin’s Lymphoma. In: Disis, M.L. (eds) Immunotherapy of Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1385/1-59745-011-1:445

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