Antitumor vaccination with gene-transduced tumor cells expressing a fusion protein RM4/IFN-tau.
Our previous studies showed that secretion of a fusion protein RM4/IFN-tau from a mouse myeloma cell line VKCK/RM4-IFN-tau curtailed its tumorigenicity. Inoculation of VKCK/RM4-IFN-tau tumor cells further induced a protective immunity against a secondary challenge of parental VKCK tumor cells, in which the predominant immune cellular components are CD8+ T cells. In this study, VKCK/RM4-IFN-tau cell line was again used to further characterize the protective immunity. We found that the reduced tumorigenicity of VKCK/RM4-IFN-tau was directly related to the amount of fusion protein secreted by tumor cells, and that CD8+ T cells derived from mice experienced with VKCK/RM4-IFN-tau tumor regression played an important role in the protective immunity in a chromium release assay in vitro and in an animal study in vivo by using T-cell subset depleted mice. Our animal studies also showed that not only the cytotoxic but also the memory T cells against the secondary challenge of parental VKCK cells could be adoptively transferred to normal BALB/c mice. In addition, our animal studies further showed that local vaccination of irradiated VKCK/RM4-IFN-tau cells was able to significantly inhibit established tumors in early stages in vivo. This study thus highlights the potential utility of this engineered VKCK/RM4-IFN-tau tumor cells secreting the fusion protein RM4/IFN-tau in cancer gene therapy.
Xiang
J
J
Saskatoon Cancer Center, Department of Microbiology, College of Medicine, University of Saskatchewan, Canada.
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D015316:Genetic Therapy; D006023:Glycoproteins / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000235:genetics*; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000628:therapy*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D014611:Vaccination
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006023:Glycoproteins; D007140:Immunoglobulin Fab Fragments; D011993:Recombinant Fusion Proteins; C047052:tumor-associated antigen 72; D007371:Interferon-gamma