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Vaccination strategies in follicular lymphoma

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Abstract

Follicular lymphoma is one of the most immuneresponsive cancers. The clonal tumor immunoglobulin expressed on the surface of malignant B cells, termed idiotype, has been used as a tumor-specific antigen in therapeutic vaccination strategies for follicular lymphoma and other B-cell malignancies. A number of phase 1 and phase 2 clinical trials have established the safety and immunogenicity of idiotype vaccine in follicular lymphoma. Three randomized, double-blind, controlled phase 3 clinical trials have recently been completed to definitively evaluate the clinical benefit of idiotype vaccine in follicular lymphoma. This review focuses on the results of these idiotype vaccine trials and discusses poten tial strategies to enhance the efficacy of vaccines in the future.

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References and Recommended Reading

  1. Gandhi MK, Marcus RE: Follicular lymphoma: time for a re-think? Blood Rev 2005, 19:165–178.

    PubMed  Google Scholar 

  2. Hiddemann W, Kneba M, Dreyling M, et al.: Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 2005, 106, 3725–3732.

    Article  PubMed  CAS  Google Scholar 

  3. Fisher RI, LeBlanc M, Press OW, et al.: New treatment options have changed the survival of patients with follicular lymphoma. J Clin Oncol 2005, 23:8447–8452.

    Article  PubMed  CAS  Google Scholar 

  4. Czuczman MS, Weaver R, Alkuzweny B, et al.: 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, 22:4711–4716.

    Article  PubMed  CAS  Google Scholar 

  5. Horning SJ, Rosenberg SA: The natural history of initially untreated low-grade non-Hodgkin’s lymphomas. N Engl J Med 1984, 311:1471–1475.

    PubMed  CAS  Google Scholar 

  6. Dave SS, Wright G, Tan B, et al.: Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med 2004, 351:2159–2169.

    Article  PubMed  CAS  Google Scholar 

  7. Wahlin BE, Sander B, Christensson B, Kimby E: CD8+ T-cell content in diagnostic lymph nodes measured by flow cytometry is a predictor of survival in follicular lymphoma. Clin Cancer Res 2007, 13:388–397.

    Article  PubMed  CAS  Google Scholar 

  8. Alvaro T, Lejeune M, Salvadó MT, et al.: Immunohistochemical patterns of reactive microenvironment are associated with clinicobiologic behavior in follicular lymphoma patients. J Clin Oncol 2006, 24:5350–5357.

    Article  PubMed  Google Scholar 

  9. Schultze JL, Seamon MJ, Michalak S, et al.: Autologous tumor infiltrating T cells cytotoxic for follicular lymphoma cells can be expanded in vitro. Blood 1997, 89:3806–3816.

    PubMed  CAS  Google Scholar 

  10. Lee ST, Liu S, Radvanyi L, et al.: A novel strategy for rapid and efficient isolation of human tumor-specific CD4(+) and CD8(+) T-cell clones. J Immunol Methods 2008, 331:13–26.

    Article  PubMed  CAS  Google Scholar 

  11. Stevenson GT, Stevenson FK: Antibody to a molecularly defined antigen confined to a tumour cell surface. Nature 1975, 254:714–716.

    Article  PubMed  CAS  Google Scholar 

  12. Stevenson GT, Elliott EV, Stevenson FK: Idiotypic determinants on the surface immunoglobulin of neoplastic lymphocytes: a therapeutic target. Fed Proc 1977, 36:2268–2271.

    PubMed  CAS  Google Scholar 

  13. Freedman PM, Autry JR, Tokuda S, Williams RC Jr: Tumor immunity induced by preimmunization with BALB/c mouse myeloma protein. J Natl Cancer Inst 1976, 56:735–740.

    PubMed  CAS  Google Scholar 

  14. Kaminski MS, Kitamura K, Maloney DG, et al.: Idiotype vaccination against murine B cell lymphoma. Inhibition of tumor immunity by free idiotype protein. J Immunol 1987, 138:1289–1296.

    PubMed  CAS  Google Scholar 

  15. Kwak LW, Young HA, Pennington RW, et al.: 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 U S A 1996, 93:10972–10977.

    Article  PubMed  CAS  Google Scholar 

  16. Kwak LW, Campbell MJ, Czerwinski DK, et al.: 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.

    PubMed  CAS  Google Scholar 

  17. 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.

    PubMed  CAS  Google Scholar 

  18. Bendandi M, Gocke CD, Kobrin CB, et al.: Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma. Nat Med 1999, 5:1171–1177.

    Article  PubMed  CAS  Google Scholar 

  19. Santos C, Stern L, Katz L, et al.: BiovaxID vaccine therapy of follicular lymphoma in first remission: long-term follow-up of a phase II trial and status of a controlled, randomized phase III trial [abstract 2441]. Blood (ASH Annual Meeting Abstracts) 2005, 106:Abstract 2441.

  20. Longo DL, Duffey PL, Gribben JG, et al.: Combination chemotherapy followed by an immunotoxin (anti-B4-blocked ricin) in patients with indolent lymphoma: results of a phase II study. Cancer J 2000, 6:146–150.

    PubMed  CAS  Google Scholar 

  21. Inoges S, Rodriguez-Calvillo M, Zabalegui N, et al.: Clinical benefit associated with idiotypic vaccination in patients with follicular lymphoma. J Natl Cancer Inst 2006, 98:1292–1301.

    Article  PubMed  Google Scholar 

  22. Neelapu SS, Kwak LW, Kobrin CB, et al.: Vaccine induced tumor-specific immunity despite severe B-cell depletion in mantle cell lymphoma. Nat Med 2005, 11:986–991.

    PubMed  CAS  Google Scholar 

  23. Koc O, Redfern C, Wiernik P, et al.: Extended follow-up and analysis with central radiological review of patients receiving FavId [abstract 772]. Blood (ASH Annual Meeting Abstracts) 2005, 106:772.

    Google Scholar 

  24. Schuster SJ, Neelapu SS, Gause BL, et al.: Idiotype vaccine therapy (BiovaxID) in follicular lymphoma in first complete remission: phase III clinical trial results [abstract 2]. J Clin Oncol 2009, 27(Suppl):18s.

    Google Scholar 

  25. Levy R, Robertson M, Ganjoo K, et al.: Results of a phase 3 trial evaluating safety and efficacy of specific immunotherapy, recombinant idiotype (Id) conjugated to KLH (Id-KLH) with GM-CSF, compared to non-specific immunotherapy, KLH with GM-CSF, in patients with follicular non Hodgkin’s lymphoma (fNHL) [abstract LB-204]. In Proceedings of the 99th Annual Meeting of the American Association for Cancer Research, San Diego, CA, April 12–16, 2008.

  26. Freedman A, Neelapu SS, Nichols C, et al.: Placebo-controlled phase III trial of patient-specific immunotherapy with mitumprotimut-T and granulocyte-macrophage colony-stimulating factor after rituximab in patients with follicular lymphoma. J Clin Oncol 2009, 27:3036–3043.

    Article  PubMed  CAS  Google Scholar 

  27. Park HJ, Neelapu SS: Developing idiotype vaccines for lymphoma: from preclinical studies to phase III clinical trials. Br J Haematol 2008, 142:179–191.

    Article  PubMed  CAS  Google Scholar 

  28. Zou W: Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer 2005, 5:263–274.

    Article  PubMed  CAS  Google Scholar 

  29. 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.

    Article  PubMed  CAS  Google Scholar 

  30. Di Nicola M, Zappasodi R, Carlo-Stella C, et al.: Vaccination with autologous tumor-loaded dendritic cells induces clinical and immunologic responses in indolent B-cell lymphoma patients with relapsed and measurable disease: a pilot study. Blood 2009, 113:18–27.

    Article  PubMed  CAS  Google Scholar 

  31. 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.

    Article  PubMed  CAS  Google Scholar 

  32. Biragyn T, Tani K, Grimm MC, et al.: Genetic fusion of chemokines to a self tumor antigen induces protective, T-cell dependent anti-tumor immunity. Nat Biotech 1999, 17:253–258.

    Article  CAS  Google Scholar 

  33. Rice J, Ottensmeier CH, Stevenson FK: DNA vaccines: precision tools for activating effective immunity against cancer. Nat Rev Cancer 2008, 8:108–120.

    Article  PubMed  CAS  Google Scholar 

  34. Neelapu SS, Gause BL, Harvey L, et al.: A novel proteoliposomal vaccine induces antitumor immunity against follicular lymphoma. Blood 2007, 109:5160–5163.

    Article  PubMed  CAS  Google Scholar 

  35. Yang ZZ, Novak AJ, Stenson MJ, et al.: Intratumoral CD4+CD25+ regulatory T-cell-mediated suppression of infiltrating CD4+ T cells in B-cell non-Hodgkin lymphoma. Blood 2006, 107:3639–3646.

    Article  PubMed  CAS  Google Scholar 

  36. Foglietta M, Delgado D, Nattamai D, et al.: CD4+Foxp3+ regulatory T cells persist in high numbers in peripheral blood after induction of clinical remission with standard chemotherapy and suppress tumor-specific effector T cells in patients with follicular lymphoma [abstract 3778]. Blood (ASH Annual Meeting Abstracts) 2008, 112:309.

    Google Scholar 

  37. Dannull J, Su Z, Rizzieri D, et al.: Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J Clin Invest 2005, 115:3623–3633.

    Article  PubMed  CAS  Google Scholar 

  38. Freeman GJ, Long AJ, Iwai Y, et al.: Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 2000, 192:1027–1034.

    Article  PubMed  CAS  Google Scholar 

  39. Nattamai D, Neelapu SS: PD-1 expression is markedly upregulated on intratumoral CD4+ and CD8+ T cells in follicular lymphoma and is associated with T-cell exhaustion [abstract 2749]. Blood (ASH Annual Meeting Abstracts) 2007, 110:Abstract 2749.

    Google Scholar 

  40. Berger R, Rotem-Yehudar R, Slama G, et al.: Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies. Clin Cancer Res 2008, 14:3044–3051.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Lymphoma and Myeloma, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 903, Houston, TX, 77030, USA

    Sattva S. Neelapu

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  1. Shibichakravarthy Kannan
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Correspondence to Sattva S. Neelapu.

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Kannan, S., Neelapu, S.S. Vaccination strategies in follicular lymphoma. Curr Hematol Malig Rep 4, 189–195 (2009). https://doi.org/10.1007/s11899-009-0025-2

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