Inhibition of established tumor growth in syngeneic mice by local inoculation of engineered mouse myeloma cells secreting a recombinant fusion protein RM4/TNF.
Mouse myeloma cell line VKCK/RM4-TNF secreting the recombinant fusion protein RM4/TNF was used to study the relationship between tumor necrosis factor (TNF) secretion of tumor cells and its tumorigenicity, and to study the potential mechanisms responsible for the antitumor immune response. To evaluate tumorigenicity, 5 x 10(5) viable TNF-secreting VKCK/RM4-TNF and non-TNF-secreting VKCK tumor cells were subcutaneously injected into BALB/c mice. Tumor progression or regression was evaluated 2 weeks after tumor inoculation. Our animal studies showed that RM4/TNF secretion by VKCK/RM4-TNF tumor cells curtailed its tumorigenicity in BALB/c mice and induced a long-term, protective immune response against a subsequent challenge of the parental VKCK tumor cells. Our animal studies in T-cell subset-depleted BALB/c mice and in T-cell-deficient nude mice demonstrated that both CD4+ and CD8+ T cells play a major role in the reduction of tumorigenicity. In addition, our results further showed that local inoculation of irradiated VKCK/RM4-TNF cells secreting TNF was able to significantly inhibit the established VKCK tumors in syngeneic mice. This study thus highlights the potential utility of engineered tumor cells secreting RM4/TNF in cancer gene therapy.
Xiang
J
J
Saskatoon Cancer Center, Department of Microbiology, University of Saskatchewan, Saskatchewan, Canada.
Qi
Y
Y
Chen
Y
Y
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D015316:Genetic Therapy / Q000379:methods; D007140:Immunoglobulin Fab Fragments / Q000096:biosynthesis* / Q000235:genetics; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D009368:Neoplasm Transplantation; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014162:Transfection; D014185:Transplantation, Isogeneic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D007140:Immunoglobulin Fab Fragments; C117771:RM4-TNF protein, recombinant; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha