Immuno-gene Therapy for Metastatic Prostate Cancer
It has long been appreciated that a significant number of prostate cancers will not progress to clinical significance, yet some prostate cancers disseminate rapidly leading to lethal metastatic disease. Therefore, a reasonable goal of prostate cancer research is to develop novel alternative interventions and adjuvant therapeutic approaches that would suppress local tumor growth and/or impact pre-existing metastatic disease. This chapter will describe the potential for gene therapy to achieve this goal. We will review both pre-clinical and clinical studies using in situ gene therapy to generate a systemic immune response. These therapeutic strategies include a cytotoxic approach using the HSV-tk gene combined with the prodrug ganciclovir, the immune modulator gene for interleukin-12, and a novel gene that is both cytotoxic and immunomodulatory, Related to Testes-specific, Vespid and Pathogenesis proteins-1 (RTVP-1).
Keywordsgene therapy prostate cancer immune therapy metastasis
Unable to display preview. Download preview PDF.
- 12.Noguchi M, Stamey TA, McNeal JE, Yemoto CM. Relationship between systematic biopsies and histological features of 222 radical prostatectomy specimens: Lack of prediction of tumor significance for men with nonpalpable prostate cancer. J Urol 2001, 166:104–109; discussion 109–110.Google Scholar
- 23.Simons JW, Mikhak B, Chang JF, DeMarzo AM, Carducci MA, Lim M 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, 59:5160–8.PubMedGoogle Scholar
- 26.Hall SJ, Mutchnik SE, Chen SH, Woo, SL, Thompson, TC. Adenovirus-mediated herpes simplex virus thymidine kinase gene and ganciclovir therapy leads to systemic activity against spontaneous and induced metastasis in an orthotopic mouse model of prostate cancer. Int J Cancer 1997:70: 183–187.PubMedCrossRefGoogle Scholar
- 27.Hall SJ, Mutchnik SE, Yang G, Timme TL, Nasu Y, Bangma CH et al. Cooperative therapeutic effects of androgen ablation and adenovirus- mediated herpes simplex virus thymidine kinase gene and ganciclovir therapy in experimental prostate cancer. Cancer Gene Ther 1999, 6:54–63.PubMedCrossRefGoogle Scholar
- 29.Timme TL, Hall SJ, Barrios R, Woo SL, Aguilar-Cordova E, Thompson TC. Local inflammatory response and vector spread after direct intraprostatic injection of a recombinant adenovirus containing the herpes simplex virus thymidine kinase gene and ganciclovir therapy in mice. Cancer Gene Ther 1998, 5:74–82.PubMedGoogle Scholar
- 38.Kuriyama S, Kikukawa M, Masui K, Okuda H, Nakatani T, Akahane T et al. Gene therapy with HSV-tk/GCV system depends on T-cell-mediated immune responses and causes apoptotic death of tumor cells in vivo. Cancer 1999, 83:374–80.Google Scholar
- 43.Teh BS, Aguilar-Cordova E, Kernen K, Chou CC, Shalev M, Vlachaki MT et al. Phase I/II trial evaluating combined radiotherapy, in situ gene therapy with or without hormonal therapy in the treatment of prostate cancer–a preliminary report. Int J Radiat Oncol Biol Phys 2001, 51:605–13.PubMedGoogle Scholar
- 45.Hull GW, McCurdy MA, Nasu Y, Bangma CH, Yang G, Shimura S et al. Prostate cancer gene therapy: Comparison of adenovirus-mediated expression of interleukin 12 with interleukin 12 plus B7-1 for in situ gene therapy and gene-modified, cell-based vaccines. Clin Cancer Res 2000, 6:4101–9.PubMedGoogle Scholar
- 47.Thompson T, Timme T, Bangma C, Nasu Y, Hull G, Hall S, Stapleton A. Molecular biology of prostate cancer, pp. 553–64. In: Comprehensive Textbook of Genitourinary Oncology. Coffey DS, Shipley WU, Vogelzang NJ, eds, Baltimore Md: Williams and Wilkins, 1999.Google Scholar
- 48.Thompson TC, Timme TL, Sehgal I. Oncogenes, growth factors, and hormones in prostate cancer, pp. 327–59. In: Hormones and Growth Factors in Development and Neoplasia. Dickson RB, Salomon DS, eds, New York: Wiley-Liss, Inc, 1998.Google Scholar