There is a critical need to develop new and effective cancer therapies that target bone, the primary metastatic site for prostate cancer and other malignancies. Among the various therapeutic approaches being considered for this application, gene-modified cell-based therapies may have specific advantages. Gene-modified cell therapy uses gene transfer and cell-based technologies in a complementary fashion to chaperone appropriate gene expression cassettes to active sites of tumor growth. In this paper, we briefly review potential cell vehicles for this approach and discuss relevant gene therapy strategies for prostate cancer. We further discuss selected studies that led to the conceptual development and preclinical testing of IL-12 gene-modified bone marrow cell therapy for prostate cancer. Finally, we discuss future directions in the development of gene-modified cell therapy for metastatic prostate cancer, including the need to identify and test novel therapeutic genes such as GLIPR1.
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American Cancer Society. Cancer Facts and Figures 2007. American Cancer Society: Atlanta, GA, 2007. Also available online. Last accessed 7 September 2007. http://www.cancer.org/downloads/STT/CAFF2007PWSecured.pdf.
Wei JT, Dunn RL, Sandler HM, McLaughlin PW, Montie JE, Litwin MS et al. Comprehensive comparison of health-related quality of life after contemporary therapies for localized prostate cancer. J Clin Oncol 2002; 20: 557–566.
Han M, Partin AW, Pound CR, Epstein JI, Walsh PC . Long-term biochemical disease-free and cancer-specific survival following anatomic radical retropubic prostatectomy. The 15-year Johns Hopkins experience. Urol Clin North Am 2001; 28: 555–565.
Trachtenberg J . A review of hormonal treatment in advanced prostate cancer. Can J Urol 1997; 4: 61–64.
Mathew P, Fidler IJ, Logothetis CJ . Combination docetaxel and platelet-derived growth factor receptor inhibition with imatinib mesylate in prostate cancer. Semin Oncol 2004; 31: 24–29.
Cross D, Burmester JK . Gene therapy for cancer treatment: past, present and future. Clin Med Res 2006; 4: 218–227.
Rosenberg SA, Yang JC, Restifo NP . Cancer immunotherapy: moving beyond current vaccines. Nat Med 2004; 10: 909–915.
Di Carlo E, Forni G, Lollini P, Colombo MP, Modesti A, Musiani P . The intriguing role of polymorphonuclear neutrophils in antitumor reactions. Blood 2001; 97: 339–345.
Serakinci N, Keith WN . Therapeutic potential of adult stem cells. Eur J Cancer 2006; 42: 1243–1246.
Yee C . Adoptive T-cell therapy of cancer. Hematol Oncol Clin North Am 2006; 20: 711–733.
Bordignon C, Yu SF, Smith CA, Hantzopoulos P, Ungers GE, Keever CA et al. Retroviral vector-mediated high-efficiency expression of adenosine deaminase (ADA) in hematopoietic long-term cultures of ADA-deficient marrow cells. Proc Natl Acad Sci USA 1989; 86: 6748–6752.
McNeel DG . Prostate cancer immunotherapy. Curr Opin Urol 2007; 17: 175–181.
Rodolfo M, Bassi C, Salvi C, Parmiani G . Therapeutic use of a long-term cytotoxic T cell line recognizing a common tumour-associated antigen: the pattern of in vitro reactivity predicts the in vivo effect on different tumours. Cancer Immunol Immunother 1991; 34: 53–62.
Mayordomo JI, Zorina T, Storkus WJ, Zitvogel L, Celluzzi C, Falo LD et al. Bone marrow-derived dendritic cells pulsed with synthetic tumour peptides elicit protective and therapeutic antitumour immunity. Nat Med 1995; 1: 1297–1302.
Rooney CM, Smith CA, Ng CY, Loftin SK, Sixbey JW, Gan Y et al. Infusion of cytotoxic T cells for the prevention and treatment of Epstein–Barr virus-induced lymphoma in allogeneic transplant recipients. Blood 1998; 92: 1549–1555.
Riddell SR . Finding a place for tumor-specific T cells in targeted cancer therapy. J Exp Med 2004; 200: 1533–1537.
Clay TM, Custer MC, Sachs J, Hwu P, Rosenberg SA, Nishimura MI . Efficient transfer of a tumor antigen-reactive TCR to human peripheral blood lymphocytes confers anti-tumor reactivity. J Immunol 1999; 163: 507–513.
Kjaergaard J, Shu S . Tumor infiltration by adoptively transferred T cells is independent of immunologic specificity but requires down-regulation of L-selectin expression. J Immunol 1999; 163: 751–759.
Chang AE, Li Q, Bishop DK, Normolle DP, Redman BD, Nickoloff BJ . Immunogenetic therapy of human melanoma utilizing autologous tumor cells transduced to secrete granulocyte–macrophage colony-stimulating factor. Hum Gene Ther 2000; 11: 839–850.
Yee C, Riddell SR, Greenberg PD . In vivo tracking of tumor-specific T cells. Curr Opin Immunol 2001; 13: 141–146.
Basse PH, Whiteside TL, Herberman RB . Use of activated natural killer cells for tumor immunotherapy in mouse and human. Methods Mol Biol 2000; 121: 81–94.
deMagalhaes-Silverman M, Donnenberg A, Lembersky B, Elder E, Lister J, Rybka W et al. Posttransplant adoptive immunotherapy with activated natural killer cells in patients with metastatic breast cancer. J Immunother (1997) 2000; 23: 154–160.
Bingle L, Brown NJ, Lewis CE . The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol 2002; 196: 254–265.
Leek RD, Harris AL . Tumor-associated macrophages in breast cancer. J Mammary Gland Biol Neoplasia 2002; 7: 177–189.
Mantovani A, Bottazzi B, Colotta F, Sozzani S, Ruco L . The origin and function of tumor-associated macrophages. Immunol Today 1992; 13: 265–270.
Satoh T, Saika T, Ebara S, Kusaka N, Timme TL, Yang G et al. Macrophages transduced with an adenoviral vector expressing interleukin 12 suppress tumor growth and metastasis in a preclinical metastatic prostate cancer model. Cancer Res 2003; 63: 7853–7860.
Movsas B, Chapman JD, Horwitz EM, Pinover WH, Greenberg RE, Hanlon AL et al. Hypoxic regions exist in human prostate carcinoma. Urology 1999; 53: 11–18.
Burke B, Tang N, Corke KP, Tazzyman D, Ameri K, Wells M et al. Expression of HIF-1alpha by human macrophages: implications for the use of macrophages in hypoxia-regulated cancer gene therapy. J Pathol 2002; 196: 204–212.
MacRae E, Brown NJ, Hamdy FC, Lewis CJ . Use of macrophages to target gene therapy to hypoxic areas of prostate tumours. British Microcirculation Society Annual Meeting 2004, Abstract Booklet. British Microcirculation Society: Bristol, UK, 2004.
Sica A, Rubino L, Mancino A, Larghi P, Porta C, Rimoldi M et al. Targeting tumour-associated macrophages. Expert Opin Ther Targets 2007; 11: 1219–1229.
Wysocki PJ, Grabarczyk P, Mackiewicz-Wysocka M, Kowalczyk DW, Mackiewicz A . Genetically modified dendritic cells—a new, promising cancer treatment strategy? Expert Opin Biol Ther 2002; 2: 835–845.
Kikuchi T . Genetically modified dendritic cells for therapeutic immunity. Tohoku J Exp Med 2006; 208: 1–8.
Ribas A . Genetically modified dendritic cells for cancer immunotherapy. Curr Gene Ther 2005; 5: 619–628.
Pereira RF, Halford KW, O’Hara MD, Leeper DB, Sokolov BP, Pollard MD et al. Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage, and lung in irradiated mice. Proc Natl Acad Sci USA 1995; 92: 4857–4861.
Sato A, Imaizumi M, Noro T, Ichinohasama R, Saito T, Yoshinari M et al. Aberrant progenitors common to megakaryocytic and myeloid cells in a Down's infant with transient abnormal myelopoiesis. Leuk Res 1995; 19: 811–815.
Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC . Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 1996; 183: 1797–1806.
Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275: 964–967.
Prockop DJ . Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 1997; 276: 71–74.
Ferrari G, Cusella-De Angelis G, Coletta M, Paolucci E, Stornaiuolo A, Cossu G et al. Muscle regeneration by bone marrow-derived myogenic progenitors. Science 1998; 279: 1528–1530.
Shamblott MJ, Axelman J, Wang S, Bugg EM, Littlefield JW, Donovan PJ et al. Derivation of pluripotent stem cells from cultured human primordial germ cells. Proc Natl Acad Sci USA 1998; 95: 13726–13731.
Shi Q, Rafii S, Wu MH, Wijelath ES, Yu C, Ishida A et al. Evidence for circulating bone marrow-derived endothelial cells. Blood 1998; 92: 362–367.
Bittner RE, Schofer C, Weipoltshammer K, Ivanova S, Streubel B, Hauser E et al. Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice. Anat Embryol (Berl) 1999; 199: 391–396.
Bjornson CR, Rietze RL, Reynolds BA, Magli MC, Vescovi AL . Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. Science 1999; 283: 534–537.
Brustle O, Jones KN, Learish RD, Karram K, Choudhary K, Wiestler OD et al. Embryonic stem cell-derived glial precursors: a source of myelinating transplants. Science 1999; 285: 754–756.
Gussoni E, Soneoka Y, Strickland CD, Buzney EA, Khan MK, Flint AF et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 1999; 401: 390–394.
Reyes M, Lund T, Lenvik T, Aguiar D, Koodie L, Verfaillie CM . Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood 2001; 98: 2615–2625.
Iwasaki H, Akashi K . Myeloid lineage commitment from the hematopoietic stem cell. Immunity 2007; 26: 726–740.
Phinney DG, Prockop DJ . Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair—current views. Stem Cells 2007; 25: 2896–2902.
Tavassoli M, Hardy CL . Molecular basis of homing of intravenously transplanted stem cells to the marrow. Blood 1990; 76: 1059–1070.
Thomas E, Storb R, Clift RA, Fefer A, Johnson FL, Neiman PE et al. Bone-marrow transplantation (first of two parts). N Engl J Med 1975; 292: 832–843.
Brenner MK, Rill DR, Holladay MS, Heslop HE, Moen RC, Buschle M et al. Gene marking to determine whether autologous marrow infusion restores long-term haemopoiesis in cancer patients. Lancet 1993; 342: 1134–1137.
Zaboikin M, Srinivasakumar N, Schuening F . Gene therapy with drug resistance genes. Cancer Gene Ther 2006; 13: 335–345.
Budak-Alpdogan T, Banerjee D, Bertino JR . Hematopoietic stem cell gene therapy with drug resistance genes: an update. Cancer Gene Ther 2005; 12: 849–863.
Pelloso D, Cyran K, Timmons L, Williams BT, Robertson MJ . Immunological consequences of interleukin 12 administration after autologous stem cell transplantation. Clin Cancer Res 2004; 10: 1935–1942.
Gautam SC, Xu YX, Dumaguin M, Janakiraman N, Chapman RA . Interleukin-12 (IL-12) gene therapy of leukemia: immune and anti-leukemic effects of IL-12-transduced hematopoietic progenitor cells. Cancer Gene Ther 2000; 7: 1060–1068.
Kunz-Schughart LA, Knuechel R . Tumor-associated fibroblasts (part II): functional impact on tumor tissue. Histol Histopathol 2002; 17: 623–637.
Kunz-Schughart LA, Knuechel R . Tumor-associated fibroblasts (part I): active stromal participants in tumor development and progression? Histol Histopathol 2002; 17: 599–621.
Studeny M, Marini FC, Dembinski JL, Zompetta C, Cabreira-Hansen M, Bekele BN et al. Mesenchymal stem cells: potential precursors for tumor stroma and targeted-delivery vehicles for anticancer agents. J Natl Cancer Inst 2004; 96: 1593–1603.
Hall B, Dembinski J, Sasser AK, Studeny M, Andreeff M, Marini F . Mesenchymal stem cells in cancer: tumor-associated fibroblasts and cell-based delivery vehicles. Int J Hematol 2007; 86: 8–16.
Nakamizo A, Marini F, Amano T, Khan A, Studeny M, Gumin J et al. Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas. Cancer Res 2005; 65: 3307–3318.
Studeny M, Marini FC, Champlin RE, Zompetta C, Fidler IJ, Andreeff M . Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors. Cancer Res 2002; 62: 3603–3608.
Khakoo AY, Finkel T . Endothelial progenitor cells. Annu Rev Med 2005; 56: 79–101.
Bengel FM, Schachinger V, Dimmeler S . Cell-based therapies and imaging in cardiology. Eur J Nucl Med Mol Imaging 2005; 32 (Suppl 2): S404–S416.
Galiano RD, Tepper OM, Pelo CR, Bhatt KA, Callaghan M, Bastidas N et al. Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells. Am J Pathol 2004; 164: 1935–1947.
Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 1999; 85: 221–228.
Moore XL, Lu J, Sun L, Zhu CJ, Tan P, Wong MC . Endothelial progenitor cells’ ‘homing’ specificity to brain tumors. Gene Therapy 2004; 11: 811–818.
Lapidot T, Dar A, Kollet O . How do stem cells find their way home? Blood 2005; 106: 1901–1910.
Kucia M, Reca R, Miekus K, Wanzeck J, Wojakowski W, Janowska-Wieczorek A et al. Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis. Stem Cells 2005; 23: 879–894.
Gazitt Y . Homing and mobilization of hematopoietic stem cells and hematopoietic cancer cells are mirror image processes, utilizing similar signaling pathways and occurring concurrently: circulating cancer cells constitute an ideal target for concurrent treatment with chemotherapy and antilineage-specific antibodies. Leukemia 2004; 18: 1–10.
Li L, Neaves WB . Normal stem cells and cancer stem cells: the niche matters. Cancer Res 2006; 66: 4553–4557.
Takahashi K, Yamanaka S . Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 663–676.
Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131: 861–872.
Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S et al. Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells. Science 2007; 318: 1917–1920.
Merritt JA, Roth JA, Logothetis CJ . Clinical evaluation of adenoviral-mediated p53 gene transfer: review of INGN 201 studies. Semin Oncol 2001; 28: 105–114.
Pisters LL, Pettaway CA, Troncoso P, McDonnell TJ, Stephens LC, Wood CG et al. Evidence that transfer of functional p53 protein results in increased apoptosis in prostate cancer. Clin Cancer Res 2004; 10: 2587–2593.
Honda T, Kagawa S, Spurgers KB, Gjertsen BT, Roth JA, Fang B et al. A recombinant adenovirus expressing wild-type Bax induces apoptosis in prostate cancer cells independently of their Bcl-2 status and androgen sensitivity. Cancer Biol Ther 2002; 1: 163–167.
Lowe SL, Rubinchik S, Honda T, McDonnell TJ, Dong JY, Norris JS . Prostate-specific expression of Bax delivered by an adenoviral vector induces apoptosis in LNCaP prostate cancer cells. Gene Therapy 2001; 8: 1363–1371.
Zhang Y, Yu J, Unni E, Shao TC, Nan B, Snabboon T et al. Monogene and polygene therapy for the treatment of experimental prostate cancers by use of apoptotic genes bax and bad driven by the prostate-specific promoter ARR(2)PB. Hum Gene Ther 2002; 13: 2051–2064.
Krygier S, Djakiew D . Neurotrophin receptor p75(NTR) suppresses growth and nerve growth factor-mediated metastasis of human prostate cancer cells. Int J Cancer 2002; 98: 1–7.
Satoh T, Timme TL, Saika T, Ebara S, Yang G, Wang J et al. Adenoviral vector-mediated mRTVP-1 gene therapy for prostate cancer. Hum Gene Ther 2003; 14: 91–101.
Figueiredo ML, Kao C, Wu L . Advances in preclinical investigation of prostate cancer gene therapy. Mol Ther 2007; 15: 1053–1064.
Herman JR, Adler HL, Aguilar-Cordova E, Rojas-Martinez A, Woo S, Timme TL et al. In situ gene therapy for adenocarcinoma of the prostate: a phase I clinical trial. Hum Gene Ther 1999; 10: 1239–1249.
Freytag SO, Khil M, Stricker H, Peabody J, Menon M, DePeralta-Venturina M et al. Phase I study of replication-competent adenovirus-mediated double suicide gene therapy for the treatment of locally recurrent prostate cancer. Cancer Res 2002; 62: 4968–4976.
Freytag SO, Stricker H, Pegg J, Paielli D, Pradhan DG, Peabody J et al. Phase I study of replication-competent adenovirus-mediated double-suicide 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 2003; 63: 7497–7506.
Teh BS, Aguilar-Cordova E, Kernen K, Chou C, Shalev M, Vlachaki MT et al. Phase I/II trial evaluating combined radiotherapy and 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: 605–613.
Freytag SO, Movsas B, Aref I, Stricker H, Peabody J, Pegg J et al. Phase I trial of replication-competent adenovirus-mediated suicide gene therapy combined with IMRT for prostate cancer. Mol Ther 2007; 15: 1016–1023.
Mullen JT, Tanabe KK . Viral oncolysis for malignant liver tumors. Ann Surg Oncol 2003; 10: 596–605.
Bischoff JR, Kirn DH, Williams A, Heise C, Horn S, Muna M et al. An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science 1996; 274: 373–376.
Wiman KG . Strategies for therapeutic targeting of the p53 pathway in cancer. Cell Death Differ 2006; 13: 921–926.
Rodriguez R, Schuur ER, Lim HY, Henderson GA, Simons JW, Henderson DR . Prostate attenuated replication competent adenovirus (ARCA) CN706: a selective cytotoxic for prostate-specific antigen-positive prostate cancer cells. Cancer Res 1997; 57: 2559–2563.
Sanda MG, Smith DC, Charles LG, Hwang C, Pienta KJ, Schlom J et al. Recombinant vaccinia-PSA (PROSTVAC) can induce a prostate-specific immune response in androgen-modulated human prostate cancer. Urology 1999; 53: 260–266.
Miller AM, Ozenci V, Kiessling R, Pisa P . Immune monitoring in a phase 1 trial of a PSA DNA vaccine in patients with hormone-refractory prostate cancer. J Immunother 2005; 28: 389–395.
Gregor PD, Wolchok JD, Turaga V, Latouche JB, Sadelain M, Bacich D et al. Induction of autoantibodies to syngeneic prostate-specific membrane antigen by xenogeneic vaccination. Int J Cancer 2005; 116: 415–421.
Peshwa MV, Shi JD, Ruegg C, Laus R, van Schooten WC . Induction of prostate tumor-specific CD8+ cytotoxic T-lymphocytes in vitro using antigen-presenting cells pulsed with prostatic acid phosphatase peptide. Prostate 1998; 36: 129–138.
Pantuck AJ, van Ophoven A, Gitlitz BJ, Tso CL, Acres B, Squiban P et al. Phase I trial of antigen-specific gene therapy using a recombinant vaccinia virus encoding MUC-1 and IL-2 in MUC-1-positive patients with advanced prostate cancer. J Immunother 2004; 27: 240–253.
Fossa A, Alsoe L, Crameri R, Funderud S, Gaudernack G, Smeland EB . Serological cloning of cancer/testis antigens expressed in prostate cancer using cDNA phage surface display. Cancer Immunol Immunother 2004; 53: 431–438.
Antonia S, Mule JJ, Weber JS . Current developments of immunotherapy in the clinic. Curr Opin Immunol 2004; 16: 130–136.
Belldegrun A, Tso CL, Zisman A, Naitoh J, Said J, Pantuck AJ et al. Interleukin 2 gene therapy for prostate cancer: phase I clinical trial and basic biology. Hum Gene Ther 2001; 12: 883–892.
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: 5160–5168.
Wislez M, Fleury-Feith J, Rabbe N, Moreau J, Cesari D, Milleron B et al. Tumor-derived granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor prolong the survival of neutrophils infiltrating bronchoalveolar subtype pulmonary adenocarcinoma. Am J Pathol 2001; 159: 1423–1433.
Hofstra CL, Van Ark I, Hofman G, Kool M, Nijkamp FP, Van Oosterhout AJ . Prevention of Th2-like cell responses by coadministration of IL-12 and IL-18 is associated with inhibition of antigen-induced airway hyperresponsiveness, eosinophilia, and serum IgE levels. J Immunol 1998; 161: 5054–5060.
Trinchieri G, Pflanz S, Kastelein RA . The IL-12 family of heterodimeric cytokines: new players in the regulation of T cell responses. Immunity 2003; 19: 641–644.
Jacobsen SE . IL12, a direct stimulator and indirect inhibitor of haematopoiesis. Res Immunol 1995; 146: 506–514.
Lenzi R, Edwards R, June C, Seiden MV, Garcia ME, Rosenblum M et al. Phase II study of intraperitoneal recombinant interleukin-12 (rhIL-12) in patients with peritoneal carcinomatosis (residual disease <1 cm) associated with ovarian cancer or primary peritoneal carcinoma. J Transl Med 2007; 5: 66.
Weiss JM, Subleski JJ, Wigginton JM, Wiltrout RH . Immunotherapy of cancer by IL-12-based cytokine combinations. Expert Opin Biol Ther 2007; 7: 1705–1721.
Wysocka M, Newton S, Benoit BM, Introcaso C, Hancock AS, Chehimi J et al. Synthetic imidazoquinolines potently and broadly activate the cellular immune response of patients with cutaneous T-cell lymphoma: synergy with interferon-gamma enhances production of interleukin-12. Clin Lymphoma Myeloma 2007; 7: 524–534.
Wang H, Yang G, Timme TL, Fujita T, Naruishi K, Frolov A et al. IL-12 gene-modified bone marrow cell therapy suppresses the development of experimental metastatic prostate cancer. Cancer Gene Ther 2007; 14: 819–827.
Fujita T, Timme TL, Tabata K, Naruishi K, Kusaka N, Watanabe M et al. Cooperative effects of adenoviral vector-mediated interleukin 12 gene therapy with radiotherapy in a preclinical model of metastatic prostate cancer. Gene Therapy 2007; 14: 227–236.
Nasu Y, Bangma CH, Hull GW, Lee HM, Hu J, Wang J et al. Adenovirus-mediated interleukin-12 gene therapy for prostate cancer: suppression of orthotopic tumor growth and pre-established lung metastases in an orthotopic model. Gene Therapy 1999; 6: 338–349.
Ren C, Li L, Goltsov AA, Timme TL, Tahir SA, Wang J et al. mRTVP-1, a novel p53 target gene with proapoptotic activities. Mol Cell Biol 2002; 22: 3345–3357.
Murphy EV, Zhang Y, Zhu W, Biggs J . The human glioma pathogenesis-related protein is structurally related to plant pathogenesis-related proteins and its gene is expressed specifically in brain tumors. Gene 1995; 159: 131–135.
Rich T, Chen P, Furman F, Huynh N, Israel MA . RTVP-1, a novel human gene with sequence similarity to genes of diverse species, is expressed in tumor cell lines of glial but not neuronal origin. Gene 1996; 180: 125–130.
Gingras MC, Margolin JF . Differential expression of multiple unexpected genes during U937 cell and macrophage differentiation detected by suppressive subtractive hybridization. Exp Hematol 2000; 28: 65–76.
Szyperski T, Fernandez C, Mumenthaler C, Wuthrich K . Structure comparison of human glioma pathogenesis-related protein GliPR and the plant pathogenesis-related protein P14a indicates a functional link between the human immune system and a plant defense system. Proc Natl Acad Sci USA 1998; 95: 2262–2266.
Ren C, Li L, Yang G, Timme TL, Goltsov A, Ren C et al. RTVP-1, a tumor suppressor inactivated by methylation in prostate cancer. Cancer Res 2004; 64: 969–976.
Naruishi K, Timme TL, Kusaka N, Fujita T, Yang G, Goltsov A et al. Adenoviral vector-mediated RTVP-1 gene-modified tumor cell-based vaccine suppresses the development of experimental prostate cancer. Cancer Gene Ther 2006; 13: 658–663.
Li L, Abdel Fattah E, Cao G, Ren C, Yang G, Goltsov AA et al. Glioma pathogenesis-related protein 1 exerts tumor suppressor activities through proapoptotic reactive oxygen species-c-Jun-NH2 kinase signaling. Cancer Res 2008; 68: 434–443.
Xu YX, Gao X, Janakiraman N, Chapman RA, Gautam SC . IL-12 gene therapy of leukemia with hematopoietic progenitor cells without the toxicity of systemic IL-12 treatment. Clin Immunol 2001; 98: 180–189.
Nishioka Y, Hirao M, Robbins PD, Lotze MT, Tahara H . Induction of systemic and therapeutic antitumor immunity using intratumoral injection of dendritic cells genetically modified to express interleukin 12. Cancer Res 1999; 59: 4035–4041.
Stewart FM, Crittenden RB, Lowry PA, Pearson-White S, Quesenberry PJ . Long-term engraftment of normal and post-5-fluorouracil murine marrow into normal nonmyeloablated mice. Blood 1993; 81: 2566–2571.
Luznik L, Slansky JE, Jalla S, Borrello I, Levitsky HI, Pardoll DM et al. Successful therapy of metastatic cancer using tumor vaccines in mixed allogeneic bone marrow chimeras. Blood 2003; 101: 1645–1652.
Bubnic SJ, Keating A . Donor stem cells home to marrow efficiently and contribute to short- and long-term hematopoiesis after low-cell-dose unconditioned bone marrow transplantation. Exp Hematol 2002; 30: 606–611.
Voest EE, Kenyon BM, O’Reilly MS, Truitt G, D’Amato RJ, Folkman J . Inhibition of angiogenesis in vivo by interleukin 12. J Natl Cancer Inst 1995; 87: 581–586.
Duda DG, Sunamura M, Lozonschi L, Kodama T, Egawa S, Matsumoto G et al. Direct in vitro evidence and in vivo analysis of the antiangiogenesis effects of interleukin 12. Cancer Res 2000; 60: 1111–1116.
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Wang, H., Thompson, T. Gene-modified bone marrow cell therapy for prostate cancer. Gene Ther 15, 787–796 (2008). https://doi.org/10.1038/gt.2008.37
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