Abstract
Gene therapy of cancer includes strategies for augmentation of immunotherapeutic and chemoterapeutic approaches. These strategies mainly involve ex vivo and in vivo cytokine gene transfer, drug sensitization with genes for prodrug delivery, and the use of drug-resistance genes for protecting bone marrow from high-dose chemotherapy (1). Vector development remains the primary focus for any future research in the field. Retroviral vectors, especially those derived from Moloney murine leukemia virus (MoMLV), remain among the most widely utilized vectors in gene therapy trials.
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References
Roth, J. A. and Cristiano, R. J. (1997) Gene therapy for cancer: what have we done and where are we going? J. Natl. Cancer Inst. 89, 21–39.
Miller, D. G., Adam, M. A., and Miller, A. D. (1990) Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection (published erratum appears in Mol. Cell. Biol. 1992,12,433). Mol. Cell. Biol. 10, 4239–4242.
Chen S. H., Kosai K., Xu B., et al. (1996) Combination suicide and cytokine gene therapy for hepatic metastases of colon carcinoma: sustained antitumor immunity prolongs animal survival. Cancer Res. 56, 3758–3762.
Saleh, M. (1997) A retroviral vector that allows efficient co-expression of two genes and the versatility of alternate selection markers. Hum. Gene Ther. 8, 979–983.
Hsieh, C. L., Chen, B. F., Wang, C. C., Liu, H. H., Chen, D. S., and Hwang L. H. (1995) Improved gene expression by a modified bicistronic retroviral vector. Biochem. Biophys. Res. Commun. 214, 910–917.
Sugimoto Y., Aksentijevich I., Gottesman M. M., and Pastan I. (1994) Efficient expression of drug-selectable genes in retroviral vectors under control of an internal ribosome entry site. Biotechnology 12, 694–698.
Freeman, S. M., Ramesh, R., Shastri, M., Munshi, A., Jensen, A. K., and Marrogi, A. J. (1995) The role of cytokines in mediating the bystander effect using HSV-tK xenogeneic cells. Cancer Lett. 92, 167–174.
Culver, K. W. (1996) Gene therapy for malignant neoplasms of the CNS. Bone Marrow Transplant 18, S6–9.
Gagandeep, S., Brew, R., Green, B., et al. (1996) Prodrug-activated gene therapy: involvement of an immunological component in the "e;bystander effect."e; Cancer Gene Ther. 3, 83–88.
Yamamoto, S., Suzuki, S., Hoshino, A., Akimoto, M., and Shimada, T. (1997) Herpes simplex virus thymidine kinase/ganciclovir-mediated killing of tumor cell induces tumor-specific cytotoxic T cells in mice. Cancer Gene Ther. 4, 91–96.
Meazza, R., Marciano, S., Sforzini, S., et al. (1996) Analysis of IL-2 receptor expression and of the biological effects of IL-2 gene transfection in small-cell lung cancer. Br. J. Cancer 74, 788–795.
Corrias, M. V., Basso, S., Meazza, R., Musiani, P., Occhino, M., Ferrini, S., and Pistoia, V. (1998) Characterization and tumorigeniticy of human neuroblastoma cells transfected with the IL-2 gene. Cancer Gene Ther. 5, 38–44.
Tjuvajev, J., Gansbacher, B., Desai, R., et al. (1995) RG-2 glioma growth attenuation and severe brain edema caused by local production of interleukin-2 and interferon-gamma. Cancer Res. 55, 1902–1910.
Bi, W. L., Parysek, L. M., Warnick, R., and Stambrook, P. J. (1993) In vitro evidence that metabolic cooperation is responsible for the bystander effect observed with HSV tk retroviral gene therapy. Hum. Gene Ther. 4, 725–731.
Freeman, S. M., Abboud, C. N., Whartenby, K. A., et al. (1993) The "e;bystander effect"e;: tumor regression when a fraction of the tumor mass is genetically modified. Cancer Res. 53, 5274–5283.
Elshami, A. A., Saavedra, A., Zhang, H., et al. (1996) Gap junctions play a role in the "e;bystander effect"e; of the herpes simplex virus thymidine kinase/ganciclovir system in vitro. Gene Ther. 3, 85–92.
Hamel, W., Magnelli, L., Chiarugi, V. P., and Israel, M. A. (1996) Herpes simplex virus thymidine kinase/ganciclovir-mediated apoptotic death of bystander cells. Cancer Res. 56, 2697–2702.
Palù, G., Cavaggioni, A., Calvi, P., Franchin, E., Pizzato, M., Boschetto, R., et al. (1999) Gene therapy of glioblastoma multiforme via combined expression of suicide and cytokine genes: a pilot study in humans. Gene Ther. 6, 330–337.
Melani, C., Chiodoni, C., Arienti, F., et al. (1994) Cytokine gene transduction in tumor cells: interleukin (IL)-2 or IL-4 gene transfer in human melanoma cells. Nat. Immun. 13, 76–84.
Sambrook, J., Fritsch, E. F., and Maniatis, T. (1989) Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, pp. 1–110.
Karnofsky, D. A. and Burchenal, J. H. (1945) The clinical evaluation of chemiotherapeutic agents in cancer, in Evaluation of Chemiotherapeutic Agents (McLeod, C. M., ed.), Columbia University Press, New York.
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Palù, G., Pizzato, M., Bonaguro, R., Colombo, F. (2000). Gene Therapy of Glioblastoma Multiforme with a Bicistronic Retroviral Vector Expressing Human IL-2 and HSV-tK . In: Walther, W., Stein, U. (eds) Gene Therapy of Cancer. Methods in Molecular Medicine™, vol 35. Humana Press. https://doi.org/10.1385/1-59259-086-1:511
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DOI: https://doi.org/10.1385/1-59259-086-1:511
Publisher Name: Humana Press
Print ISBN: 978-0-89603-714-4
Online ISBN: 978-1-59259-086-5
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