Abstract
Despite recent advances in early detection and conventional therapies, prostate cancer continues to be the second-leading cause of cancer mortality in American men. Advanced prostate cancer progresses, metastasizes, and becomes resistant to treatment. Clinical evaluation of gene therapy for prostate cancer has demonstrated its safety, and early success warrants further study. In combination with conventional therapies, which are limited by treatment-related morbidity and toxicity, molecular therapy for advanced prostate cancer shows great promise. In this chapter, we review the current status of gene therapy approaches for prostate cancer, which include corrective gene therapy, oncolytic viral therapy, cytotoxic gene therapy, and immunotherapy.
Key Words
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Jemal, A., Murray, T., Ward, E., et al. (2005). Cancer statistics, 2005. CA Cancer J. Clin. 55, 10–30.
Coen, J. J., Zietman, A. L., Thakral, H., and Shipley, W. U. (2002). Radical radiation for localized prostate cancer: local persistence of disease results in a late wave of metastases. J. Clin. Oncol. 20, 3199–3205.
Han, M., Partin, A. W., Pound, C. R., Epstein, J. I., and Walsh, P. C. (2001). Long-term biochemical disease-free and cancer-specific survival following anatomic radical retropubic prostatectomy. The 15-year Johns Hopkins experience. Urol. Clin. North. Am. 28, 555–565.
Chodak, G. W., Keane, T., and Klotz, L. (2002). Critical evaluation of hormonal therapy for carcinoma of the prostate. Urology 60, 201–208.
Petrylak, D. P., Tangen, C. M., Hussain, M. H., et al. (2004). Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N. Engl. J. Med. 351, 1513–1520.
Tannock, I. F., deWit, R., Berry, W. R., et al. (2004). Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N. Engl. J. Med. 351, 1502–1512.
Worgall, S., Wolff, G., Falck-Pedersen, E., and Crystal, R. G. (1997). Innate immune mechanisms dominate elimination of adenoviral vectors following in vivo administration. Hum. Gene Ther. 8, 37–44.
Chirmule, N., Propert, K., Magosin, S., Qian, Y., Qian, R., and Wilson, J. (1999). Immune responses to adenovirus and adeno-associated virus in humans. Gene Ther. 6, 1574–1583.
Schiedner, G., Morral, N., Parks, R. J., et al. (1998). Genomic DNA transfer with a high-capacity adenovirus vector results in improved in vivo gene expression and decreased toxicity. Nat. Genet. 18, 180–183.
Hearing, P., Samulski, R. J., Wishart, W. L., and Shenk, T. (1987). Identification of a repeated sequence element required for efficient encapsidation of the adenovirus type 5 chromosome. J. Virol. 61, 2555–2558.
Nevins, J. R. (1981). Mechanism of activation of early viral transcription by the adenovirus E1A gene product. Cell 26, 213–220.
Rich, D. P., Couture, L. A., Cardoza, L. M., et al. (1993). Development and analysis of recombinant adenoviruses for gene therapy of cystic fibrosis. Hum. Gene Ther. 4, 461–476.
Bagchi, S., Raychaudhuri, P., and Nevins, J. R. (1990). Adenovirus E1A proteins can dissociate heteromeric complexes involving the E2F transcription factor: a novel mechanism for E1A trans-activation. Cell 62, 659–669.
Mal, A., Poon, R. Y., Howe, P. H., Toyoshima, H., Hunter, T., and Harter, M. L. (1996). Inactivation of p27Kip1 by the viral E1A oncoprotein in TGFbeta-treated cells. Nature 380, 262–265.
Somasundaram, K. and El-Deiry, W. S. (1997). Inhibition of p53-mediated transactivation and cell cycle arrest by E1A through its p300/CBP-interacting region. Oncogene 14, 1047–1057.
Rao, L., Debbas, M., Sabbatini, P., Hockenbery, D., Korsmeyer, S., and White, E. (1992). The adenovirus E1A proteins induce apoptosis, which is inhibited by the E1B 19-kDa and Bcl-2 proteins. Proc. Natl. Acad. Sci. USA 89, 7742–7746.
Halbert, D. N., Cutt, J. R., and Shenk, T. (1985). Adenovirus early region 4 encodes functions required for efficient DNA replication, late gene expression, and host cell shutoff. J. Virol. 56, 250–257.
Pilder, S., Moore, M., Logan, J., and Shenk, T. (1986). The adenovirus E1B-55K transforming polypeptide modulates transport or cytoplasmic stabilization of viral and host cell mRNAs. Mol. Cell Biol. 6, 470–476.
Nevels, M., Rubenwolf, S., Spruss, T., Wolf, H., and Dobner, T. (1997). The adenovirus E4orf6 protein can promote E1A/E1B-induced focus formation by interfering with p53 tumor suppressor function. Proc. Natl. Acad. Sci. USA 94, 1206–1211.
Field, J., Gronostajski, R. M., and Hurwitz, J. (1984). Properties of the adenovirus DNA polymerase. J. Biol. Chem. 259, 9487–9495.
Challberg, M. D., Desiderio, S. V., and Kelly, T. J.,Jr. (1980). Adenovirus DNA replication in vitro: characterization of a protein covalently linked to nascent DNA strands. Proc. Natl. Acad. Sci. USA 77, 5105–5109.
Burgert, H. G., Maryanski, J. L., and Kvist, S. (1987). “E3/19K” protein of adenovirus type 2 inhibits lysis of cytolytic T lymphocytes by blocking cell-surface expression of histocompatibility class I antigens. Proc. Natl. Acad. Sci. USA 84, 1356–1360.
Elsing, A. and Burgert, H. G. (1998). The adenovirus E3/10.4K-14.5K proteins down-modulate the apoptosis receptor Fas/Apo-1 by inducing its internalization. Proc. Natl. Acad. Sci. USA 95, 10,072–10,077.
Mathews, M. B. and Shenk, T. (1991). Adenovirus virus-associated RNA and translation control. J. Virol. 65, 5657–5662.
Leibowitz, J. and Horwitz, M. S. (1975). Synthesis and assembly of adenovirus polypeptides. III. Reversible inhibition of hexon assembly in adenovirus type 5 temperature-sensitive mutants. Virology 66, 10–24.
Bergelson, J. M., Cunningham, J. A., Droguett, G., et al. (1997). Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science 275, 1320–1323.
Wickham, T. J., Mathias, P., Cheresh, D. A., and Nemerow, G. R. (1993). Integrins alpha v beta 3 and alpha v beta 5 promote adenovirus internalization but not virus attachment. Cell 73, 309–319.
Tollefson, A. E., Scaria, A., Hermiston, T. W., Ryerse, J. S., Wold, L. J., and Wold, W. S. (1996). The adenovirus death protein (E3-11.6K) is required at very late stages of infection for efficient cell lysis and release of adenovirus from infected cells. J. Virol. 70, 2296–2306.
Doronin, K., Toth, K., Kuppuswamy, M., Ward, P., Tollefson, A. E., and Wold, W. S. (2000). Tumor-specific, replication-competent adenovirus vectors overexpressing the adenovirus death protein. J. Virol. 74, 6147–6155.
Rauen, K. A., Sudilovsky, D., Le, J. L., et al. (2002). Expression of the coxsackie adenovirus receptor in normal prostate and in primary and metastatic prostate carcinoma: potential relevance to gene therapy. Cancer Res. 62, 3812–3818.
Douglas, J. T., Rogers, B. E., Rosenfeld, M. E., Michael, S. I., Feng, M., and Curiel, D. T. (1996). Targeted gene delivery by tropism-modified adenoviral vectors. Nat. Biotechnol. 14, 1574–1578.
Wickham, T. J., Segal, D. M., Roelvink, P. W., et al. (1996). Targeted adenovirus gene transfer to endothelial and smooth muscle cells by using bispecific antibodies. J. Virol. 70, 6831–6838.
Kraaij, R., van Rijswijk, A. L., Oomen, M. H., Haisma, H. J., and Bangma, C. H. (2005). Prostate specific membrane antigen (PSMA) is a tissue-specific target for adenoviral transduction of prostate cancer in vitro. Prostate 62, 253–259.
Wickham, T. J., Roelvink, P. W., Brough, D. E., and Kovesdi, I. (1996). Adenovirus targeted to heparan-containing receptors increases its gene delivery efficiency to multiple cell types. Nat. Biotechnol. 14, 1570–1573.
Krasnykh, V., Dmitriev, I., Mikheeva, G., Miller, C. R., Belousova, N., and Curiel, D. T. (1998). Characterization of an adenovirus vector containing a heterologous peptide epitope in the HI loop of the fiber knob. J. Virol. 72, 1844–1852.
Lupold, S. E. and Rodriguez, R. (2004). Disulfide-constrained peptides that bind to the extracellular portion of the prostate-specific membrane antigen. Mol. Cancer Ther. 3, 597–603.
Shayakhmetov, D. M., Papayannopoulou, T., Stamatoyannopoulos, G., and Lieber, A. (2000). Efficient gene transfer into human CD34(+) cells by a retargeted adenovirus vector. J. Virol. 74, 2567–2583.
Gaggar, A., Shayakhmetov, D. M., and Lieber, A. (2003). CD46 is a cellular receptor for group B adenoviruses. Nat. Med. 9, 1408–1412.
Sova, P., Ren, X. W., Ni, S., et al. (2004). A tumor-targeted and conditionally replicating oncolytic adenovirus vector expressing TRAIL for treatment of liver metastases. Mol. Ther. 9, 496–509.
Kotin, R. M., Siniscalco, M., Samulski, R. J., et al. (1990). Site-specific integration by adeno-associated virus. Proc. Natl. Acad. Sci. USA 87, 2211–2215.
Linden, R. M., Ward, P., Giraud, C., Winocour, E., and Berns, K. I. (1996). Site-specific integration by adeno-associated virus. Proc. Natl. Acad. Sci. USA 93, 11,288–11,294.
Kearns, W. G., Afione, S. A., Fulmer, S. B., et al. (1996). Recombinant adeno-associated virus (AAV-CFTR) vectors do not integrate in a site-specific fashion in an immortalized epithelial cell line. Gene Ther. 3, 748–755.
Rolling, F. and Samulski, R. J. (1995). AAV as a viral vector for human gene therapy. Generation of recombinant virus. Mol. Biotechnol. 3, 9–15.
Urabe, M., Ding, C., and Kotin, R. M. (2002). Insect cells as a factory to produce adeno-associated virus type 2 vectors. Hum. Gene Ther. 13, 1935–1943.
Ferrari, F. K., Samulski, T., Shenk, T., and Samulski, R. J. (1996). Second-strand synthesis is a rate-limiting step for efficient transduction by recombinant adeno-associated virus vectors. J Virol 70, 3227–3234.
McCarty, D. M., Monahan, P. E., and Samulski, R. J. (2001). Self-complementary recombinant adeno-associated virus (scAAV) vectors promote efficient transduction independently of DNA synthesis. Gene Ther. 8, 1248–1254.
Warrington, K. H.,Jr., Gorbatyuk, O. S., Harrison, J. K., Opie, S. R., Zolotukhin, S., and Muzyczka, N. (2004). Adenoassociated virus type 2 VP2 capsid protein is nonessential and can tolerate large peptide insertions at its N terminus. J. Virol. 78, 6595–6609.
Recchia, A., Perani, L., Sartori, D., Olgiati, C., and Mavilio, F. (2004). Site-specific integration of functional transgenes into the human genome by adeno/AAV hybrid vectors. Mol. Ther. 10, 660–670.
Brand, K., Arnold, W., Bartels, T., et al. (1997). Liver-associated toxicity of the HSV-tk/GCV approach and adenoviral vectors. Cancer Gene Ther. 4, 9–16.
Herman, J. R., Adler, H. L., Aguilar-Cordova, E., et al. (1999). In situ gene therapy for adenocarcinoma of the prostate: a phase I clinical trial. Hum. Gene Ther. 10, 1239–1249.
Stamey, T. A., Yang, N., Hay, A. R., McNeal, J. E., Freiha, F. S., and Redwine, E. (1987). Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N. Engl. J. Med. 317, 909–916.
Riegman, P. H., Vlietstra, R. J., van der Korput, J. A., Romijn, J. C., and Trapman, J. (1989). Characterization of the prostate-specific antigen gene: a novel human kallikrein-like gene. Biochem. Biophys. Res. Commun. 159, 95–102.
Cleutjens, K. B., van der Korput, H. A., van Eekelen, C. C., vanRooij, H. C., Faber, P. W., and Trapman, J. (1997). An androgen response element in a far upstream enhancer region is essential for high, androgen-regulated activity of the prostate-specific antigen promoter. Mol. Endocrinol. 11, 148–161.
Pang, S., Dannull, J., Kaboo, R., et al. (1997). Identification of a positive regulatory element responsible for tissuespecific expression of prostate-specific antigen. Cancer Res. 57, 495–499.
Schuur, E. R., Henderson, G. A., Kmetec, L. A., Miller, J. D., Lamparski, H. G., and Henderson, D. R. (1996). Prostatespecific antigen expression is regulated by an upstream enhancer. J. Biol. Chem. 271, 7043–7051.
Riegman, P. H., Vlietstra, R. J., van der Korput, J. A., Brinkmann, A. O., and Trapman, J. (1991). The promoter of the prostate-specific antigen gene contains a functional androgen responsive element. Mol. Endocrinol. 5, 1921–1930.
Gotoh, A., Ko, S. C., Shirakawa, T., et al. (1998). Development of prostate-specific antigen promoter-based gene therapy for androgen-independent human prostate cancer. J. Urol. 160, 220–229.
Lu, Y., Carraher, J., Zhang, Y., et al. (1999). Delivery of adenoviral vectors to the prostate for gene therapy. Cancer Gene Ther. 6, 64–72.
Yeung, F., Li, X., Ellett, J., Trapman, J., Kao, C., and Chung, L. W. (2000). Regions of prostate-specific antigen (PSA) promoter confer androgen-independent expression of PSA in prostate cancer cells. J. Biol. Chem. 275, 40,846–40,855.
Wu, L., Matherly, J., Smallwood, A., et al. (2001). Chimeric PSA enhancers exhibit augmented activity in prostate cancer gene therapy vectors. Gene Ther. 8, 1416–1426.
Latham, J. P., Searle, P. F., Mautner, V., and James, N. D. (2000). Prostate-specific antigen promoter/enhancer driven gene therapy for prostate cancer: construction and testing of a tissue-specific adenovirus vector. Cancer Res. 60, 334–341.
Horoszewicz, J. S., Kawinski, E., and Murphy, G. P. (1987). Monoclonal antibodies to a new antigenic marker in epithelial prostatic cells and serum of prostatic cancer patients. Anticancer Res. 7, 927–935.
Pinto, J. T., Suffoletto, B. P., Berzin, T. M., et al. (1996). Prostate-specific membrane antigen: a novel folate hydrolase in human prostatic carcinoma cells. Clin. Cancer Res. 2, 1445–1451.
Carter, R. E., Feldman, A. R., and Coyle, J. T. (1996). Prostate-specific membrane antigen is a hydrolase with substrate and pharmacologic characteristics of a neuropeptidase. Proc. Natl. Acad. Sci. USA 93, 749–753.
Pangalos, M. N., Neefs, J. M., Somers, M., et al. (1999). Isolation and expression of novel human glutamate carboxypeptidases with N-acetylated alpha-linked acidic dipeptidase and dipeptidyl peptidase IV activity. J. Biol. Chem. 274, 8470–8483.
Silver, D. A., Pellicer, I., Fair, W. R., Heston, W. D., and Cordon-Cardo, C. (1997). Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin. Cancer Res. 3, 81–85.
Xiao, Z., Adam, B. L., Cazares, L. H., et al. (2001). Quantitation of serum prostate-specific membrane antigen by a novel protein biochip immunoassay discriminates benign from malignant prostate disease. Cancer Res. 61, 6029–6033.
Sweat, S. D., Pacelli, A., Murphy, G. P., and Bostwick, D. G. (1998). Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases. Urology 52, 637–640.
Wright, G. L.,Jr., Grob, B. M., Haley, C., et al. (1996). Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy. Urology 48, 326–334.
O’Keefe, D. S., Su, S. L., Bacich, D. J., et al. (1998). Mapping, genomic organization and promoter analysis of the human prostate-specific membrane antigen gene. Biochim. Biophys. Acta 1443, 113–127.
Watt, F., Martorana, A., Brookes, D. E., et al. (2001). A tissue-specific enhancer of the prostate-specific membrane antigen gene, FOLH1. Genomics 73, 243–254.
Lee, S. J., Lee, K., Yang, X., et al. (2003). NFATc1 with AP-3 site binding specificity mediates gene expression of prostate-specific-membrane-antigen. J. Mol. Biol. 330, 749–760.
Uchida, A., O’Keefe, D. S., Bacich, D. J., Molloy, P. L., and Heston, W. D. (2001). In vivo suicide gene therapy model using a newly discovered prostate-specific membrane antigen promoter/enhancer: a potential alternative approach to androgen deprivation therapy. Urology 58, 132–139.
Lee, S. J., Zhang, Y., Lee, S. D., et al. (2004). Targeting prostate cancer with conditionally replicative adenovirus using PSMA enhancer. Mol. Ther. 10, 1051–1058.
Lee, S. J., Kim, H. S., Yu, R., et al. (2002). Novel prostate-specific promoter derived from PSA and PSMA enhancers. Mol. Ther. 6, 415–421.
Li, X., Zhang, Y. P., Kim, H. S., et al. (2005). Gene therapy for prostate cancer by controlling adenovirus E1a and E4 gene expression with PSES enhancer. Cancer Res. 65, 1941–1951.
Pan, L. C. and Price, P. A. (1984). The effect of transcriptional inhibitors on the bone gamma-carboxyglutamic acid protein response to 1,25-dihydroxyvitamin D3 in osteosarcoma cells. J. Biol. Chem. 259, 5844–5847.
Jung, C., Ou, Y. C., Yeung, F., Frierson, H. F.,Jr., and Kao, C. (2001). Osteocalcin is incompletely spliced in nonosseous tissues. Gene 271, 143–150.
Wu, T. T., Sikes, R. A., Cui, Q., et al. (1998). Establishing human prostate cancer cell xenografts in bone: induction of osteoblastic reaction by prostate-specific antigen-producing tumors in athymic and SCID/bg mice using LNCaP and lineage-derived metastatic sublines. Int. J. Cancer 77, 887–894.
Koeneman, K. S., Yeung, F., and Chung, L. W. (1999). Osteomimetic properties of prostate cancer cells: a hypothesis supporting the predilection of prostate cancer metastasis and growth in the bone environment. Prostate 39, 246–261.
Bortell, R., Owen, T. A., Bidwell, J. P., et al. (1992). Vitamin D-responsive protein-DNA interactions at multiple promoter regulatory elements that contribute to the level of rat osteocalcin gene expression. Proc. Natl. Acad. Sci. USA 89, 6119–6123.
Lian, J. B., Stein, G. S., Stein, J. L., and vanWijnen, A. J. (1999). Regulated expression of the bone-specific osteocalcin gene by vitamins and hormones. Vitam. Horm. 55, 443–509.
Banerjee, C., Stein, J. L., VanWijnen, A. J., Frenkel, B., Lian, J. B., and Stein, G. S. (1996). Transforming growth factor-beta 1 responsiveness of the rat osteocalcin gene is mediated by an activator protein-1 binding site. Endocrinology 137, 1991–2000.
Banerjee, C., Hiebert, S. W., Stein, J. L., Lian, J. B., and Stein, G. S. (1996). An AML-1 consensus sequence binds an osteoblast-specific complex and transcriptionally activates the osteocalcin gene. Proc. Natl. Acad. Sci. USA 93, 4968–4973.
Ko, S. C., Cheon, J., Kao, C., et al. (1996). Osteocalcin promoter-based toxic gene therapy for the treatment of osteosarcoma in experimental models. Cancer Res. 56, 4614–4619.
Koeneman, K. S., Kao, C., Ko, S. C., et al. (2000). Osteocalcin-directed gene therapy for prostate-cancer bone metastasis. World J. Urol. 18, 102–110.
Kubo, H., Gardner, T. A., Wada, Y., et al. (2003). Phase I dose escalation clinical trial of adenovirus vector carrying osteocalcin promoter-driven herpes simplex virus thymidine kinase in localized and metastatic hormone-refractory prostate cancer. Hum. Gene Ther. 14, 227–241.
Chiu, C. P. and Harley, C. B. (1997). Replicative senescence and cell immortality: the role of telomeres and telomerase. Proc. Soc. Exp. Biol. Med. 214, 99–106.
Kim, N. W., Piatyszek, M. A., Prowse, K. R., et al. (1994). Specific association of human telomerase activity with immortal cells and cancer. Science 266, 2011–2015.
Horikawa, I., Cable, P. L., Afshari, C., and Barrett, J. C. (1999). Cloning and characterization of the promoter region of human telomerase reverse transcriptase gene. Cancer Res. 59, 826–830.
Sommerfeld, H. J., Meeker, A. K., Piatyszek, M. A., Bova, G. S., Shay, J. W., and Coffey, D. S. (1996). Telomerase activity: a prevalent marker of malignant human prostate tissue. Cancer Res. 56, 218–222.
Lin, T., Huang, X., Gu, J., et al. (2002). Long-term tumor-free survival from treatment with the GFP-TRAIL fusion gene expressed from the hTERT promoter in breast cancer cells. Oncogene 21, 8020–8028.
Gu, J., Andreeff, M., Roth, J. A., and Fang, B. (2002). hTERT promoter induces tumor-specific Bax gene expression and cell killing in syngenic mouse tumor model and prevents systemic toxicity. Gene Ther. 9, 30–37.
Kawashima, T., Kagawa, S., Kobayashi, N., et al. (2004). Telomerase-specific replication-selective virotherapy for human cancer. Clin. Cancer Res. 10, 285–292.
Thompson, I. M., Goodman, P. J., Tangen, C. M., et al. (2003). The influence of finasteride on the development of prostate cancer. N. Engl. J. Med. 349, 215–224.
Office of Biotechnology Activities’ Recombinant DNA and Gene Transfer Web Page, http://www4.od.nih.gov/oba/rdna.htm.
Levine, A. J. (1997). p53, the cellular gatekeeper for growth and division. Cell 88, 323–331.
Sherr, C. J. (1996). Cancer cell cycles. Science 274, 1672–1677.
Downing, S. R., Russell, P. J., and Jackson, P. (2003). Alterations of p53 are common in early stage prostate cancer. Can. J. Urol. 10, 1924–1933.
Eastham, J. A., Stapleton, A. M., Gousse, A. E., et al. (1995). Association of p53 mutations with metastatic prostate cancer. Clin. Cancer Res. 1, 1111–1118.
Yang, C., Cirielli, C., Capogrossi, M. C., and Passaniti, A. (1995). Adenovirus-mediated wild-type p53 expression induces apoptosis and suppresses tumorigenesis of prostatic tumor cells. Cancer Res. 55, 4210–4213.
Eastham, J. A., Hall, S. J., Sehgal, I., et al. (1995). In vivo gene therapy with p53 or p21 adenovirus for prostate cancer. Cancer Res. 55, 5151–5155.
Ko, S. C., Gotoh, A., Thalmann, G. N., et al. (1996). Molecular therapy with recombinant p53 adenovirus in an androgen-independent, metastatic human prostate cancer model. Hum. Gene Ther. 7, 1683–1691.
Eastham, J. A., Grafton, W., Martin, C. M., and Williams, B. J. (2000). Suppression of primary tumor growth and the progression to metastasis with p53 adenovirus in human prostate cancer. J. Urol. 164, 814–819.
Hernandez, I., Maddison, L. A., Wei, Y., et al. (2003). Prostate-specific expression of p53(R172L) differentially regulates p21, Bax, and mdm2 to inhibit prostate cancer progression and prolong survival. Mol. Cancer Res. 1, 1036–1047.
Gurnani, M., Lipari, P., Dell, J., Shi, B., and Nielsen, L. L. (1999). Adenovirus-mediated p53 gene therapy has greater efficacy when combined with chemotherapy against human head and neck, ovarian, prostate, and breast cancer. Cancer Chemother. Pharmacol. 44, 143–151.
Colletier, P. J., Ashoori, F., Cowen, D., et al. (2000). Adenoviral-mediated p53 transgene expression sensitizes both wild-type and null p53 prostate cancer cells in vitro to radiation. Int. J. Radiat. Oncol. Biol. Phys. 48, 1507–1512.
Sasaki, R., Shirakawa, T., Zhang, Z. J., et al. (2001). Additional gene therapy with Ad5CMV-p53 enhanced the efficacy of radiotherapy in human prostate cancer cells. Int. J. Radiat. Oncol. Biol. Phys. 51, 1336–1345.
Cowen, D., Salem, N., Ashoori, F., et al. (2000). Prostate cancer radiosensitization in vivo with adenovirus-mediated p53 gene therapy. Clin. Cancer Res. 6, 4402–4408.
Pantuck, A. J., Zisman, A., and Belldegrun, A. S. (2000). Gene therapy for prostate cancer at the University of California, Los Angeles: preliminary results and future directions. World J. Urol. 18, 143–147.
Sweeney, P. and Pisters, L. L. (2000). Ad5CMVp53 gene therapy for locally advanced prostate cancer-where do we stand? World J. Urol. 18, 121–124.
Maki, C. G. (1999). Oligomerization is required for p53 to be efficiently ubiquitinated by MDM2. J. Biol. Chem. 274, 16,531–16,535.
Fuchs, S. Y., Adler, V., Buschmann, T., Wu, X., and Ronai, Z. (1998). Mdm2 association with p53 targets its ubiquitination. Oncogene 17, 2543–2547.
Haupt, Y., Maya, R., Kazaz, A., and Oren, M. (1997). Mdm2 promotes the rapid degradation of p53. Nature 387, 296–299.
Kussie, P. H., Gorina, S., Marechal, V., et al. (1996). Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science 274, 948–953.
Leite, K. R., Franco, M. F., Srougi, M., et al. (2001). Abnormal expression of MDM2 in prostate carcinoma. Mod. Pathol. 14, 428–436.
Zhang, Z., Li, M., Wang, H., Agrawal, S., and Zhang, R. (2003). Antisense therapy targeting MDM2 oncogene in prostate cancer: Effects on proliferation, apoptosis, multiple gene expression, and chemotherapy. Proc. Natl. Acad. Sci. USA 100, 11,636–11,641.
Wang, H., Oliver, P., Zhang, Z., Agrawal, S., and Zhang, R. (2003). Chemosensitization and radiosensitization of human cancer by antisense anti-MDM2 oligonucleotides: in vitro and in vivo activities and mechanisms. Ann. NY Acad. Sci. 1002, 217–235.
Zhang, Z., Wang, H., Prasad, G., et al. (2004). Radiosensitization by antisense anti-MDM2 mixed-backbone oligonucleotide in in vitro and in vivo human cancer models. Clin. Cancer Res. 10, 1263–1273.
Mu, Z., Hachem, P., Agrawal, S., and Pollack, A. (2004). Antisense MDM2 oligonucleotides restore the apoptotic response of prostate cancer cells to androgen deprivation. Prostate 60, 187–196.
Maehama, T. and Dixon, J. E. (1998). The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J. Biol. Chem. 273, 13,375–13,378.
McMenamin, M. E., Soung, P., Perera, S., Kaplan, I., Loda, M., and Sellers, W. R. (1999). Loss of PTEN expression in paraffin-embedded primary prostate cancer correlates with high Gleason score and advanced stage. Cancer Res. 59, 4291–4296.
Burgering, B. M. and Kops, G. J. (2002). Cell cycle and death control: long live Forkheads. Trends Biochem. Sci. 27, 352–360.
Kotelevets, L., vanHengel, J., Bruyneel, E., Mareel, M., van Roy, F., and Chastre, E. (2001). The lipid phosphatase activity of PTEN is critical for stabilizing intercellular junctions and reverting invasiveness. J. Cell Biol. 155, 1129–1135.
Stambolic, V., Suzuki, A., de la Pompa, J. L., et al. (1998). Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 95, 29–39.
Zundel, W., Schindler, C., Haas-Kogan, D., et al. (2000). Loss of PTEN facilitates HIF-1-mediated gene expression. Genes Dev. 14, 391–396.
Davies, M. A., Kim, S. J., Parikh, N. U., Dong, Z., Bucana, C. D., and Gallick, G. E. (2002). Adenoviral-mediated expression of MMAC/PTEN inhibits proliferation and metastasis of human prostate cancer cells. Clin. Cancer Res. 8, 1904–1914.
Rosser, C. J., Tanaka, M., Pisters, L. L., et al. (2004). Adenoviral-mediated PTEN transgene expression sensitizes Bcl-2-expressing prostate cancer cells to radiation. Cancer Gene Ther. 11, 273–279.
Tanaka, M., Rosser, C. J., and Grossman, H. B. (2005). PTEN gene therapy induces growth inhibition and increases efficacy of chemotherapy in prostate cancer. Cancer Detect Prev. 29, 170–174.
Jarrard, D. F., Bova, G. S., Ewing, C. M., et al. (1997). Deletional, mutational, and methylation analyses of CDKN2 (p16/MTS1) in primary and metastatic prostate cancer. Genes Chromosomes Cancer 19, 90–96.
Liggett, W. H.,Jr. and Sidransky, D. (1998). Role of the p16 tumor suppressor gene in cancer. J. Clin. Oncol. 16, 1197–1206.
Isaacs, W. B. (1995). Molecular genetics of prostate cancer. Cancer Surv. 25, 357–379.
Steiner, M. S., Zhang, Y., Farooq, F., Lerner, J., Wang, Y., and Lu, Y. (2000). Adenoviral vector containing wild-type p16 suppresses prostate cancer growth and prolongs survival by inducing cell senescence. Cancer Gene Ther. 7, 360–372.
Allay, J. A., Steiner, M. S., Zhang, Y., Reed, C. P., Cockroft, J., and Lu, Y. (2000). Adenovirus p16 gene therapy for prostate cancer. World J. Urol. 18, 111–120.
Gotoh, A., Kao, C., Ko, S. C., Hamada, K., Liu, T. J., and Chung, L. W. (1997). Cytotoxic effects of recombinant adenovirus p53 and cell cycle regulator genes (p21 WAF1/CIP1 and p16CDKN4) in human prostate cancers. J. Urol. 158, 636–641.
Deng, J., Xia, W., and Hung, M. C. (1998). Adenovirus 5 E1A-mediated tumor suppression associated with E1Amediated apoptosis in vivo. Oncogene 17, 2167–2175.
Bischoff, J. R., Kirn, D. H., Williams, A., et al. (1996). An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science 274, 373–376.
Heise, C., Sampson-Johannes, A., Williams, A., McCormick, F., Von Hoff, D. D., and Kirn, D. H. (1997). ONYX-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherapeutic agents. Nat. Med. 3, 639–645.
Heise, C. C., Williams, A. M., Xue, S., Propst, M., and Kirn, D. H. (1999). Intravenous administration of ONYX-015, a selectively replicating adenovirus, induces antitumoral efficacy. Cancer Res. 59, 2623–2628.
Ganly, I., Kirn, D., Eckhardt, G., et al. (2000). A phase I study of Onyx-015, an E1B attenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer. Clin. Cancer Res. 6, 798–806.
Nemunaitis, J., Khuri, F., Ganly, I., et al. (2001). Phase II trial of intratumoral administration of ONYX-015, a replication-selective adenovirus, in patients with refractory head and neck cancer. J. Clin. Oncol. 19, 289–298.
Khuri, F. R., Nemunaitis, J., Ganly, I., et al. (2000). A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer. Nat. Med. 6, 879–885.
Hecht, J. R., Bedford, R., Abbruzzese, J. L., et al. (2003). A phase I/II trial of intratumoral endoscopic ultrasound injection of ONYX-015 with intravenous gemcitabine in unresectable pancreatic carcinoma. Clin. Cancer Res. 9, 555–561.
Morley, S., MacDonald, G., Kirn, D., Kaye, S., Brown, R., and Soutar, D. (2004). The dl1520 virus is found preferentially in tumor tissue after direct intratumoral injection in oral carcinoma. Clin. Cancer Res. 10, 4357–4362.
Reid, T. R., Freeman, S., Post, L., McCormick, F., and Sze, D. Y. (2005). Effects of Onyx-015 among metastatic colorectal cancer patients that have failed prior treatment with 5-FU/leucovorin. Cancer Gene Ther. 12, 673–681
Mulvihill, S., Warren, R., Venook, A., et al. (2001). Safety and feasibility of injection with an E1B-55 kDa genedeleted, replication-selective adenovirus (ONYX-015) into primary carcinomas of the pancreas: a phase I trial. Gene Ther. 8, 308–315.
Nemunaitis, J., Ganly, I., Khuri, F., et al. (2000). Selective replication and oncolysis in p53 mutant tumors with ONYX-015, an E1B-55kD gene-deleted adenovirus, in patients with advanced head and neck cancer: a phase II trial. Cancer Res. 60, 6359–6366.
Goodrum, F. D. and Ornelles, D. A. (1998). p53 status does not determine outcome of E1B 55-kilodalton mutant adenovirus lytic infection. J. Virol. 72, 9479–9490.
Rothmann, T., Hengstermann, A., Whitaker, N. J., Scheffner, M., and zur Hausen, H. (1998). Replication of ONYX-015, a potential anticancer adenovirus, is independent of p53 status in tumor cells. J. Virol. 72, 9470–9478.
Edwards, S. J., Dix, B. R., Myers, C. J., et al. (2002). Evidence that replication of the antitumor adenovirus ONYX-015 is not controlled by the p53 and p14(ARF) tumor suppressor genes. J. Virol. 76, 12,483–12,490.
O’Shea, C. C., Johnson, L., Bagus, B., et al. (2004). Late viral RNA export, rather than p53 inactivation, determines ONYX-015 tumor selectivity. Cancer Cell 6, 611–623.
Freytag, S. O., Rogulski, K. R., Paielli, D. L., Gilbert, J. D., and Kim, J. H. (1998). A novel three-pronged approach to kill cancer cells selectively: concomitant viral, double suicide gene, and radiotherapy. Hum. Gene Ther. 9, 1323–1333.
Rodriguez, R., Schuur, E. R., Lim, H. Y., Henderson, G. A., Simons, J. W., and Henderson, D. R. (1997). Prostate attenuated replication competent adenovirus (ARCA) CN706: a selective cytotoxic for prostate-specific antigen-positive prostate cancer cells. Cancer Res. 57, 2559–2563.
DeWeese, T. L., van der Poel, H., Li, S., et al. (2001). A phase I trial of CV706, a replication-competent, PSA selective oncolytic adenovirus, for the treatment of locally recurrent prostate cancer following radiation therapy. Cancer Res. 61, 7464–7472.
Yu, D. C., Chen, Y., Seng, M., Dilley, J., and Henderson, D. R. (1999). The addition of adenovirus type 5 region E3 enables calydon virus 787 to eliminate distant prostate tumor xenografts. Cancer Res. 59, 4200–4203.
Dilley, J., Reddy, S., Ko, D., et al. (2005). Oncolytic adenovirus CG7870 in combination with radiation demonstrates synergistic enhancements of antitumor efficacy without loss of specificity. Cancer Gene Ther. 12, 715–722
Yu, D. C., Chen, Y., Dilley, J., et al. (2001). Antitumor synergy of CV787, a prostate cancer-specific adenovirus, and paclitaxel and docetaxel. Cancer Res. 61, 517–525.
Matsubara, S., Wada, Y., Gardner, T. A., et al. (2001). A conditional replication-competent adenoviral vector, Ad-OCE1a, to cotarget prostate cancer and bone stroma in an experimental model of androgen-independent prostate cancer bone metastasis. Cancer Res. 61, 6012–6019.
Hsieh, C. L., Yang, L., Miao, L., et al. (2002). A novel targeting modality to enhance adenoviral replication by vitamin D(3) in androgen-independent human prostate cancer cells and tumors. Cancer Res. 62, 3084–3092.
Yu, D. C., Sakamoto, G. T., and Henderson, D. R. (1999). Identification of the transcriptional regulatory sequences of human kallikrein 2 and their use in the construction of calydon virus 764, an attenuated replication competent adenovirus for prostate cancer therapy. Cancer Res. 59, 1498–1504.
Konety, B. R., Johnson, C. S., Trump, D. L., and Getzenberg, R. H. (1999). Vitamin D in the prevention and treatment of prostate cancer. Semin. Urol. Oncol. 17, 77–84.
Getzenberg, R. H., Light, B. W., Lapco, P. E., et al. (1997). Vitamin D inhibition of prostate adenocarcinoma growth and metastasis in the Dunning rat prostate model system. Urology 50, 999–1006.
Zhao, X. Y. and Feldman, D. (2001). The role of vitamin D in prostate cancer. Steroids 66, 293–300.
Doronin, K., Kuppuswamy, M., Toth, K., et al. (2001). Tissue-specific, tumor-selective, replication-competent adenovirus vector for cancer gene therapy. J. Virol. 75, 3314–3324.
Banerjee, N. S., Rivera, A. A., Wang, M., et al. (2004). Analyses of melanoma-targeted oncolytic adenoviruses with tyrosinase enhancer/promoter-driven E1A, E4, or both in submerged cells and organotypic cultures. Mol. Cancer Ther. 3, 437–449.
Huang, X. and Lee, C. (2003). From TGF-beta to cancer therapy. Curr. Drug Targets 4, 243–250.
Narumoto, K., Saibara, T., Maeda, T., et al. (2000). Transforming growth factor-beta 1 derived from biliary epithelial cells may attenuate alloantigen-specific immune responses. Transpl. Int. 13, 21–27.
Ke, B., Coito, A. J., Kato, H., et al. (2000). Fas ligand gene transfer prolongs rat renal allograft survival and downregulates anti-apoptotic Bag-1 in parallel with enhanced Th2-type cytokine expression. Transplantation 69, 1690–1694.
Winoto, A. (1997). Cell death in the regulation of immune responses. Curr. Opin. Immunol. 9, 365–370.
Norris, J. S., Hyer, M. L., Voelkel-Johnson, C., Lowe, S. L., Rubinchik, S., and Dong, J. Y. (2001). The use of Fas Ligand, TRAIL and Bax in gene therapy of prostate cancer. Curr. Gene Ther. 1, 123–136.
Harrison, D., Sauthoff, H., Heitner, S., Jagirdar, J., Rom, W. N., and Hay, J. G. (2001). Wild-type adenovirus decreases tumor xenograft growth, but despite viral persistence complete tumor responses are rarely achieved-deletion of the viral E1b-19-kD gene increases the viral oncolytic effect. Hum. Gene Ther. 12, 1323–1332.
Sauthoff, H., Hu, J., Maca, C., et al. (2003). Intratumoral spread of wild-type adenovirus is limited after local injection of human xenograft tumors: virus persists and spreads systemically at late time points. Hum. Gene Ther. 14, 425–433.
Shen, B. H. and Hermiston, T. W. (2005). Effect of hypoxia on Ad5 infection, transgene expression and replication. Gene Ther. 12, 902–910.
Jin, F., Xie, Z., Kuo, C. J., Chung, L. W., and Hsieh, C. L. (2005). Cotargeting tumor and tumor endothelium effectively inhibits the growth of human prostate cancer in adenovirus-mediated antiangiogenesis and oncolysis combination therapy. Cancer Gene Ther. 12, 257–267.
Liu, X. Y., Qiu, S. B., Zou, W. G., et al. (2005). Effective gene-virotherapy for complete eradication of tumor mediated by the combination of hTRAIL (TNFSF10) and plasminogen k5. Mol. Ther. 11, 531–541.
Culy, C. (2005). Bevacizumab: antiangiogenic cancer therapy. Drugs Today (Barc) 41, 23–26.
Mesnil, M., Piccoli, C., Tiraby, G., Willecke, K., and Yamasaki, H. (1996). Bystander killing of cancer cells by herpes simplex virus thymidine kinase gene is mediated by connexins. Proc. Natl. Acad. Sci. USA 93, 1831–1835.
Eastham, J. A., Chen, S. H., Sehgal, I., et al. (1996). Prostate cancer gene therapy: herpes simplex virus thymidine kinase gene transduction followed by ganciclovir in mouse and human prostate cancer models. Hum. Gene Ther. 7, 515–523.
Cheon, J., Kim, H. K., Moon, D. G., Yoon, D. K., Cho, J. H., and Koh, S. K. (2000). Adenovirus-mediated suicide-gene therapy using the herpes simplex virus thymidine kinase gene in cell and animal models of human prostate cancer: changes in tumour cell proliferative activity. BJU Int. 85, 759–766.
Hall, S. J., Mutchnik, S. E., Chen, S. H., Woo, S. L., and Thompson, T. C. (1997). 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 70, 183–187.
Freytag, S. O., Khil, M., Stricker, H., et al. (2002). Phase I study of replication-competent adenovirus-mediated double suicide gene therapy for the treatment of locally recurrent prostate cancer. Cancer Res. 62, 4968–4976.
Freytag, S. O., Paielli, D., Wing, M., et al. (2002). Efficacy and toxicity of replication-competent adenovirus-mediated double suicide gene therapy in combination with radiation therapy in an orthotopic mouse prostate cancer model. Int. J. Radiat. Oncol. Biol. Phys. 54, 873–885.
Freytag, S. O., Stricker, H., Pegg, J., et al. (2003). Phase I study of replication-competent adenovirus-mediated doublesuicide gene therapy in combination with conventional-dose three-dimensional conformal radiation therapy for the treatment of newly diagnosed, intermediate-to high-risk prostate cancer. Cancer Res. 63, 7497–7506.
Wiley, S. R., Schooley, K., Smolak, P. J., et al. (1995). Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3, 673–682.
Pitti, R. M., Marsters, S. A., Ruppert, S., Donahue, C. J., Moore, A., and Ashkenazi, A. (1996). Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J. Biol. Chem. 271, 12,687–12,690.
Pan, G., Ni, J., Wei, Y. F., Yu, G., Gentz, R., and Dixit, V. M. (1997). An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science 277, 815–818.
Pan, G., O’Rourke, K., Chinnaiyan, A. M., et al. (1997). The receptor for the cytotoxic ligand TRAIL. Science 276, 111–113.
Nesterov, A., Lu, X., Johnson, M., Miller, G. J., Ivashchenko, Y., and Kraft, A. S. (2001). Elevated AKT activity protects the prostate cancer cell line LNCaP from TRAIL-induced apoptosis. J. Biol. Chem. 276, 10,767–10,774.
Voelkel-Johnson, C., King, D. L., and Norris, J. S. (2002). Resistance of prostate cancer cells to soluble TNF-related apoptosis-inducing ligand (TRAIL/Apo2L) can be overcome by doxorubicin or adenoviral delivery of full-length TRAIL. Cancer Gene Ther. 9, 164–172.
Shankar, S., Singh, T. R., and Srivastava, R. K. (2004). Ionizing radiation enhances the therapeutic potential of TRAIL in prostate cancer in vitro and in vivo: Intracellular mechanisms. Prostate 61, 35–49.
Shankar, S., Chen, X., and Srivastava, R. K. (2005). Effects of sequential treatments with chemotherapeutic drugs followed by TRAIL on prostate cancer in vitro and in vivo. Prostate 62, 165–186.
Jo, M., Kim, T. H., Seol, D. W., et al. (2000). Apoptosis induced in normal human hepatocytes by tumor necrosis factor-related apoptosis-inducing ligand. Nat. Med. 6, 564–567.
Lawrence, D., Shahrokh, Z., Marsters, S., et al. (2001). Differential hepatocyte toxicity of recombinant Apo2L/TRAIL versions. Nat. Med. 7, 383–385.
Mori, E., Thomas, M., Motoki, K., et al. (2004). Human normal hepatocytes are susceptible to apoptosis signal mediated by both TRAIL-R1 and TRAIL-R2. Cell Death Differ. 11, 203–207.
Hao, C., Song, J. H., Hsi, B., et al. (2004). TRAIL inhibits tumor growth but is nontoxic to human hepatocytes in chimeric mice. Cancer Res. 64, 8502–8506.
Kaliberov, S. A., Kaliberova, L. N., Stockard, C. R., Grizzle, W. E., and Buchsbaum, D. J. (2004). Adenovirus-mediated FLT1-targeted proapoptotic gene therapy of human prostate cancer. Mol. Ther. 10, 1059–1070.
Vanoosten, R. L., Moore, J. M., Ludwig, A. T., and Griffith, T. S. (2005). Depsipeptide (FR901228) enhances the cytotoxic activity of TRAIL by redistributing TRAIL receptor to membrane lipid rafts. Mol. Ther. 11, 542–552.
Bander, N. H., Yao, D., Liu, H., et al. (1997). MHC class I and II expression in prostate carcinoma and modulation by interferon-alpha and-gamma. Prostate 33, 233–239.
Kwon, E. D., Hurwitz, A. A., Foster, B. A., et al. (1997). Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer. Proc. Natl. Acad. Sci. USA 94, 8099–8103.
Sanda, M. G., Ayyagari, S. R., Jaffee, E. M., et al. (1994). Demonstration of a rational strategy for human prostate cancer gene therapy. J. Urol. 151, 622–628.
Vieweg, J., Rosenthal, F. M., Bannerji, R., et al. (1994). Immunotherapy of prostate cancer in the Dunning rat model: use of cytokine gene modified tumor vaccines. Cancer Res. 54, 1760–1765.
Simons, J. W., Mikhak, B., Chang, J. F., et al. (1999). Induction of immunity to prostate cancer antigens: results of a clinical trial of vaccination with irradiated autologous prostate tumor cells engineered to secrete granulocytemacrophage colony-stimulating factor using ex vivo gene transfer. Cancer Res. 59, 5160–5168.
Simmons, S. J., Tjoa, B. A., Rogers, M., et al. (1999). GM-CSF as a systemic adjuvant in a phase II prostate cancer vaccine trial. Prostate 39, 291–297.
Simons, J. W., Nelson, W., Nemunaitis, J., et al. (2002). Phase II trials of a GM-CSF gene-transduced prostate cancer cell vaccine (GVAX) in hormone refractory prostate cancer. Proc. Am. Soc. Clin. Oncol. 21, 729A.
Simons, J. W., Higano, C., Corman, J., et al. (2003). A phase I/II study of high dose allogeneic GM-CSF gene-transduced prostate cancer cell line vaccine in patients with metastatic hormone-refractory prostate cancer. Proc. Am. Soc. Clin. Oncol. 22, 166A.
Tjoa, B., Boynton, A., Kenny, G., Ragde, H., Misrock, S. L., and Murphy, G. (1996). Presentation of prostate tumor antigens by dendritic cells stimulates T-cell proliferation and cytotoxicity. Prostate 28, 65–69.
Murphy, G., Tjoa, B., Ragde, H., Kenny, G., and Boynton, A. (1996). Phase I clinical trial: T-cell therapy for prostate cancer using autologous dendritic cells pulsed with HLA-A0201-specific peptides from prostate-specific membrane antigen. Prostate 29, 371–380.
Tjoa, B. A., Erickson, S. J., Bowes, V. A., et al. (1997). Follow-up evaluation of prostate cancer patients infused with autologous dendritic cells pulsed with PSMA peptides. Prostate 32, 272–278.
Tjoa, B. A., Simmons, S. J., Elgamal, A., et al. (1999). Follow-up evaluation of a phase II prostate cancer vaccine trial. Prostate 40, 125–129.
Triest, J. A., Grignon, D. J., Cher, M. L., et al. (1998). Systemic interleukin 2 therapy for human prostate tumors in a nude mouse model. Clin. Cancer Res. 4, 2009–2014.
Belldegrun, A., Tso, C. L., Zisman, A., et al. (2001). Interleukin 2 gene therapy for prostate cancer: phase I clinical trial and basic biology. Hum. Gene Ther. 12, 883–892.
Trudel, S., Trachtenberg, J., Toi, A., et al. (2003). A phase I trial of adenovector-mediated delivery of interleukin-2 (AdIL-2) in high-risk localized prostate cancer. Cancer Gene Ther. 10, 755–763.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Humana Press Inc., Totowa, NJ
About this chapter
Cite this chapter
Antonio, J., Li, X., Gardner, T.A., Kao, C. (2007). Gene Therapy for Advanced Prostate Cancer. In: Chung, L.W.K., Isaacs, W.B., Simons, J.W. (eds) Prostate Cancer. Contemporary Cancer Research. Humana Press. https://doi.org/10.1007/978-1-59745-224-3_9
Download citation
DOI: https://doi.org/10.1007/978-1-59745-224-3_9
Publisher Name: Humana Press
Print ISBN: 978-1-58829-696-2
Online ISBN: 978-1-59745-224-3
eBook Packages: MedicineMedicine (R0)