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GM-CSF Gene-Transduced Prostate Cancer Vaccines: GVAX

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Drug Management of Prostate Cancer

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Abstract

Prostate cancer offers both compelling and challenging problems for research and development of active specific immunotherapy using cancer vaccines. Vaccine strategies designed to break tolerance and generate a sustained, potent, antineoplastic immune response against prostate cancer represent a therapeutic strategy, which has emerged as a significant research enterprise over the past 15 years. Several approaches to prostate cancer immunotherapy have been investigated in the past decade, including defined peptide vaccines, dendritic cell-based vaccines, whole-tumor cell autologous and allogeneic vaccines, carbohydrate vaccines, and poxvirus vaccines. It is estimated that over 1,200 prostate cancer patients have been treated with investigational vaccines in Phase I, II, or III trials. This chapter will focus on a narrow segment of vaccine research: strategies employing GM-CSF gene-transduced whole prostate cancer cell vaccines (GVAX). Attention will be given to the preclinical rationale, clinical development, emerging body of knowledge on resistance mechanisms, clinical development challenges, and future directions for GVAX in particular. The extensive data with GVAX now in humans with advanced prostate cancer is likely to be instructive in the future research and development of antineoplastic immunotherapy for prostate cancer.

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References

  1. Jemal A, Murray T, Ward E, et al. Cancer statistics. CA Cancer J Clin 2005;55(1):10–30.

    Article  PubMed  Google Scholar 

  2. SEER Cancer Statistics Review. National Cancer Institute. Bethesda, MD; 1975–2005.http://www.seer.cancer.gov/csr/1975_2005/. Accessed 13 Feb 2009.

  3. Paulson DF, Moul JW, Walther PJ. Radical prostatectomy for clinical stage T1-2N0M0 prostatic adenocarcinoma: long-term results. J Urol 1990;144(5):1180–4.

    PubMed  CAS  Google Scholar 

  4. Stamey TA, Yemoto CM, McNeal JE, Sigal BM, Johnstone IM. Prostate cancer is highly predictable: a prognostic equation based on all morphological variables in radical prostatectomy specimens. J Urol 2000;163(4):1155–60.

    Article  PubMed  CAS  Google Scholar 

  5. Dillioglugil O, Leibman BD, Kattan MW, Seale-Hawkins C, Wheeler TM, Scardino PT. Hazard rates for progression after radical prostatectomy for clinically localized prostate cancer. Urology 1997;50(1):93–9.

    Article  PubMed  CAS  Google Scholar 

  6. Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural history of progression after PSA elevation following radical prostatectomy. JAMA 1999;281(17):1591–7.

    Article  PubMed  CAS  Google Scholar 

  7. Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004;351(15):1502–12.

    Article  PubMed  CAS  Google Scholar 

  8. Petrylak DP, Tangen CM, Hussain MH, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004;351(15):1513–20.

    Article  PubMed  CAS  Google Scholar 

  9. Lombard M, Pastoret PP, Moulin AM. A brief history of vaccines and vaccination. Rev Sci Tech 2007;26(1):29–48.

    PubMed  CAS  Google Scholar 

  10. Prehn RT, Main JM. Immunity to methylcholanthrene-induced sarcomas. J Natl Cancer Inst 1957;18(6):769–78.

    PubMed  CAS  Google Scholar 

  11. Brannen GE, Gomolka DM, Coffey DS. Specificity of cell membrane antigens in prostatic cancer. Cancer Chemother Rep 1975;59(1):127–38.

    PubMed  CAS  Google Scholar 

  12. Blades RA, Keating PJ, McWilliam LJ, George NJ, Stern PL. Loss of HLA class I expression in prostate cancer: implications for immunotherapy. Urology 1995;46(5):681–6. Discussion 686–7.

    Article  PubMed  CAS  Google Scholar 

  13. Sanda MG, Restifo NP, Walsh JC, et al. Molecular characterization of defective antigen processing in human prostate cancer. J Natl Cancer Inst 1995;87(4):280–5.

    Article  PubMed  CAS  Google Scholar 

  14. 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 U S A 1993;90(8):3539–43.

    Article  PubMed  CAS  Google Scholar 

  15. Warren TL, Weiner GJ. Uses of granulocyte-macrophage colony-stimulating factor in vaccine development. Curr Opin Hematol 2000;7(3):168–73.

    Article  PubMed  CAS  Google Scholar 

  16. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998;392(6673):245–52.

    Article  PubMed  CAS  Google Scholar 

  17. Vieweg J, Rosenthal FM, Bannerji R, et al. Immunotherapy of prostate cancer in the Dunning rat model: use of cytokine gene modified tumor vaccines. Cancer Res 1994;54:1760–5.

    PubMed  CAS  Google Scholar 

  18. Sanda MG, Ayyagari SR, Jaffee EM, et al. Demonstration of a rational strategy for human prostate cancer gene therapy. J Urol 1994;151(3):622–8.

    PubMed  CAS  Google Scholar 

  19. Moody DB, Robinson JC, Ewing CM, Lazenby AJ, Isaacs WB. Interleukin-2 transfected prostate cancer cells generate a local antitumor effect in vivo. Prostate 1994;24(5):244–51.

    Article  PubMed  CAS  Google Scholar 

  20. 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(8):1537–46.

    PubMed  CAS  Google Scholar 

  21. Simons JW, Mikhak B, Chang JF, et al. Induction of immunity to prostate cancer antigens: results of a clinical trial of vaccination with irradiated autologous prostate tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor using ex vivo gene transfer. Cancer Res 1999;59(20):5160–8.

    PubMed  CAS  Google Scholar 

  22. Emens LA, Reilly RT, Jaffee EM. Breast cancer vaccines: maximizing cancer treatment by tapping into host immunity. Endocr Relat Cancer 2005;12(1):1–17.

    Article  PubMed  CAS  Google Scholar 

  23. Simons JW, Sacks N. Granulocyte-macrophage colony-stimulating factor-transduced allogeneic cancer cellular immunotherapy: the GVAX vaccine for prostate cancer. Urol Oncol 2006;24(5):419–24.

    Article  PubMed  CAS  Google Scholar 

  24. Laheru D, Jaffee EM. Immunotherapy for pancreatic cancer – science driving clinical progress. Nat Rev 2005;5(6):459–67.

    CAS  Google Scholar 

  25. Nemunaitis J, Sterman D, Jablons D, et al. Granulocyte-macrophage colony-stimulating factor gene-modified autologous tumor vaccines in non-small-cell lung cancer. J Natl Cancer Inst 2004;96(4):326–31.

    Article  PubMed  CAS  Google Scholar 

  26. Simons JW, Carducci MA, Mikhak B, et al. Phase I/II trial of an allogeneic cellular immunotherapy in hormone-naive prostate cancer. Clin Cancer Res 2006;12(11 Pt 1):3394–401.

    Article  PubMed  CAS  Google Scholar 

  27. Simons JW, Nelson WG, Nemunaitis J, et al. Phase II trials of a GM-CSF gene-transduced prostate cancer cell line vaccine (GVAX) in hormone refractory prostate cancer. Proc Am Soc Clin Oncol 2002;21:729.

    Google Scholar 

  28. Groh V, Li YQ, Cioca D, et al. Efficient cross-priming of tumor antigen-specific T cells by dendritic cells sensitized with diverse anti-MICA opsonized tumor cells. Proc Natl Acad Sci U S A 2005;102(18):6461–6.

    Article  PubMed  CAS  Google Scholar 

  29. Wolf AM, Wolf D, Steurer M, Gastl G, Gunsilius E, Grubeck-Loebenstein B. Increase of regulatory T cells in the peripheral blood of cancer patients. Clin Cancer Res 2003;9(2):606–12.

    PubMed  Google Scholar 

  30. Walunas TL, Bluestone JA. CTLA-4 regulates tolerance induction and T cell differentiation in vivo. J Immunol 1998;160(8):3855–60.

    PubMed  CAS  Google Scholar 

  31. Parry RV, Chemnitz JM, Frauwirth KA, et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol Cell Biol 2005;25(21):9543–53.

    Article  PubMed  CAS  Google Scholar 

  32. Hurwitz AA, Foster BA, Kwon ED, et al. Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade. Cancer Res 2000;60(9):2444–8.

    PubMed  CAS  Google Scholar 

  33. Kwon ED, Foster BA, Hurwitz AA, et al. Elimination of residual metastatic prostate cancer after surgery and adjunctive cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade immunotherapy. Proc Natl Acad Sci U S A 1999;96(26):15074–9.

    Article  PubMed  CAS  Google Scholar 

  34. Kwon ED, Hurwitz AA, Foster BA, et al. Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer. Proc Natl Acad Sci U S A 1997;94(15):8099–103.

    Article  PubMed  CAS  Google Scholar 

  35. 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(7):1027–34.

    Article  PubMed  CAS  Google Scholar 

  36. Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A 2002;99(19):12293–7.

    Article  PubMed  CAS  Google Scholar 

  37. Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 2002;8(8):793–800.

    PubMed  CAS  Google Scholar 

  38. Sun J, Xu K, Wu C, et al. PD-L1 expression analysis in gastric carcinoma tissue and blocking of tumor-associated PD-L1 signaling by two functional monoclonal antibodies. Tissue Antigens 2007;69(1):19–27.

    Article  PubMed  CAS  Google Scholar 

  39. Blank C, Brown I, Peterson AC, et al. PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells. Cancer Res 2004;64(3):1140–5.

    Article  PubMed  CAS  Google Scholar 

  40. Inman BA, Sebo TJ, Frigola X, et al. PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: associations with localized stage progression. Cancer 2007;109(8):1499–505.

    Article  PubMed  CAS  Google Scholar 

  41. Roth TJ, Sheinin Y, Lohse CM, et al. B7-H3 ligand expression by prostate cancer: a novel marker of prognosis and potential target for therapy. Cancer Res 2007;67(16):7893–900.

    Article  PubMed  CAS  Google Scholar 

  42. Martin-Orozco N, Wang YH, Yagita H, Dong C. Cutting edge: programmed death (PD) ligand-1/PD-1 interaction is required for CD8+ T cell tolerance to tissue antigens. J Immunol 2006;177(12):8291–5.

    PubMed  CAS  Google Scholar 

  43. Wang L, Fraser CC, Kikly K, et al. B7-H3 promotes acute and chronic allograft rejection. Eur J Immunol 2005;35(2):428–38.

    Article  PubMed  CAS  Google Scholar 

  44. Xu J, Huang B, Xiong P, et al. Soluble mouse B7-H3 down-regulates dendritic cell stimulatory capacity to allogenic T cell proliferation and production of IL-2 and IFN-gamma. Cell Mol Immunol 2006;3(3):235–40.

    PubMed  CAS  Google Scholar 

  45. Nurieva R, Thomas S, Nguyen T, et al. T-cell tolerance or function is determined by combinatorial costimulatory signals. EMBO J 2006;25(11):2623–33.

    Article  PubMed  CAS  Google Scholar 

  46. Huang CT, Workman CJ, Flies D, et al. Role of LAG-3 in regulatory T cells. Immunity 2004;21(4):503–13.

    Article  PubMed  CAS  Google Scholar 

  47. Zhu X, Yang P, Zhou H, et al. CD4+ CD25+ Tregs express an increased LAG-3 and CTLA-4 in anterior chamber-associated immune deviation. Graefe’s Arch Clin Exp Ophthalmol 2007;245(10):1549–57.

    Article  CAS  Google Scholar 

  48. Zarek PE, Huang CT, Lutz ER, et al. A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells. Blood 2008;111(1):251–9.

    Article  PubMed  CAS  Google Scholar 

  49. Grosso JF, Kelleher CC, Harris TJ, et al. LAG-3 regulates CD8+ T cell accumulation and effector function in murine self- and tumor-tolerance systems. J Clin Invest 2007;117(11):3383–92.

    Article  PubMed  CAS  Google Scholar 

  50. Munn DH, Zhou M, Attwood JT, et al. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 1998;281(5380):1191–3.

    Article  PubMed  CAS  Google Scholar 

  51. Kudo Y, Boyd CA, Spyropoulou I, et al. Indoleamine 2,3-dioxygenase: distribution and function in the developing human placenta. J Reprod Immunol 2004;61(2):87–98.

    Article  PubMed  CAS  Google Scholar 

  52. Mellor AL, Sivakumar J, Chandler P, et al. Prevention of T cell-driven complement activation and inflammation by tryptophan catabolism during pregnancy. Nat Immunol 2001;2(1):64–8.

    Article  PubMed  CAS  Google Scholar 

  53. Munn DH, Shafizadeh E, Attwood JT, Bondarev I, Pashine A, Mellor AL. Inhibition of T cell proliferation by macrophage tryptophan catabolism. J Exp Med 1999;189(9):1363–72.

    Article  PubMed  CAS  Google Scholar 

  54. Uyttenhove C, Pilotte L, Theate I, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med 2003;9(10):1269–74.

    Article  PubMed  CAS  Google Scholar 

  55. Friberg M, Jennings R, Alsarraj M, et al. Indoleamine 2,3-dioxygenase contributes to tumor cell evasion of T cell-mediated rejection. Int J Cancer 2002;101(2):151–5.

    Article  PubMed  CAS  Google Scholar 

  56. Muller AJ, DuHadaway JB, Donover PS, Sutanto-Ward E, Prendergast GC. Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nat Med 2005;11(3):312–9.

    Article  PubMed  CAS  Google Scholar 

  57. Ou X, Cai S, Liu P, et al. Enhancement of dendritic cell-tumor fusion vaccine potency by indoleamine-pyrrole 2,3-dioxygenase inhibitor, 1-MT. J Cancer Res Clin Oncol 2008;134(5):525–33.

    Article  PubMed  CAS  Google Scholar 

  58. Nigam A, Yacavone RF, Zahurak ML, et al. Immunomodulatory properties of antineoplastic drugs administered in conjunction with GM-CSF-secreting cancer cell vaccines. Int J Oncol 1998;12(1):161–70.

    PubMed  CAS  Google Scholar 

  59. Emens LA, Jaffee EM. Leveraging the activity of tumor vaccines with cytotoxic chemotherapy. Cancer Res 2005;65(18):8059–64.

    Article  PubMed  CAS  Google Scholar 

  60. Harris TJ, Hipkiss EL, Borzillary S, et al. Radiotherapy augments the immune response to prostate cancer in a time-dependent manner. Prostate 2008;68(12):1319–29.

    Article  PubMed  Google Scholar 

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Acknowledgment

The authors acknowledge Rebecca Levine, of PCF, for her editorial and bibliographic assistance in the preparation of the manuscript.

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Authors and Affiliations

  1. Prostate Cancer Foundation, Santa Monica, CA, USA

    Jonathan W. Simons

Authors
  1. Lalit R. Patel
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  2. Jonathan W. Simons
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Correspondence to Jonathan W. Simons .

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Editors and Affiliations

  1. Medical Oncology Branch, NIH National Cancer Institute, Rockville Pike 9000, Bethesda, 20892, Maryland, USA

    William D. Figg

  2. Medical Oncology Branch, NIH National Cancer Institute, Rockville Pike 9000, Bethesda, 20892, Maryland, USA

    Cindy H. Chau

  3. School of Medicine, Dept. Urology, University of California, San Francisco, Divisadero Street 1600, San Francisco, 94115, California, USA

    Eric J. Small

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Patel, L.R., Simons, J.W. (2010). GM-CSF Gene-Transduced Prostate Cancer Vaccines: GVAX. In: Figg, W., Chau, C., Small, E. (eds) Drug Management of Prostate Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-60327-829-4_29

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  • DOI: https://doi.org/10.1007/978-1-60327-829-4_29

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