Intratumoral delivery of an interferon gamma retrovirus-producing cells inhibits growth of a murine melanoma by a non-immune mechanism.
Interferon gamma (IFNgamma) is a potent inhibitor of cell growth effective against a wide range of tumor-derived cell lines. We cloned murine IFNgamma cDNA into a retroviral vector and created a packaging cell line (Am-gamma) producing this IFNgamma-encoding retrovirus. In a pilot experiment, admixing and co-injection of equal numbers of retrovirus-producing and target B16 melanoma cells led to high rates of infection and strong suppression of neoplastic growth. This effect was observed in the absence of measurable systemic production of IFNgamma and could be reproduced in animals lacking cytotoxic immune responses. Tumor angiogenesis was unaffected and no increase in apoptosis was apparent; however, mitotic indices were greatly reduced in Am-gamma-containing abortive tumors. We thus concluded that IFNgamma directly affects proliferation of B16 cells. Indeed, exposure of B16 cells to IFNgamma in vitro inhibits cell division, as measured by a thymidine incorporation assay. Most importantly, repeated intratumoral injections of Am-gamma stunted growth of established B16 melanomas in 75% of treated animals. Thus, this approach can serve as a prototype for new anti-cancer modalities.
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Department of Pathobiology, University of Pennsylvania, 3800 Spruce Street, 368E, Philadelphia, PA 19104-6051, USA.
Thomas-Tikhonenko
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D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002455:Cell Division; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000378:metabolism; D008545:Melanoma / Q000628:therapy*; D008546:Melanoma, Experimental; D051379:Mice; D008938:Mitosis; D012190:Retroviridae / Q000235:genetics* / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007371:Interferon-gamma; D013936:Thymidine