Interleukin-2-secreting mouse fibroblasts transfected with genomic DNA from murine melanoma cells prolong the survival of mice with melanoma.
A retrovirus was used to introduce a provirus (pZipNeoSVIL-2) containing the gene for interleukin-2 (IL-2) along with a neor gene (confers resistance to G418) into LM cells, a mouse cell line expressing defined major histocompatibility complex class I antigens (H-2k). After initial selection in growth medium containing G418, IL-2 secretion was confirmed, and the cells were then cotransfected with genomic DNA from B16F1 or B16F10 melanoma cells, along with DNA from a plasmid (pHyg) that confers resistance to hygromycin. After a second round of selection in growth medium containing sufficient quantities of hygromycin to kill 100% of nontransfected cells but without further modification, the unfractionated populations of transfected cells were tested for their immunotherapeutic properties in C57BL/6 mice (H-2b) with established B16 melanomas (H-2b). Animals with melanomas treated with either of the transfected cell populations survived significantly (P < 0.01) longer than untreated mice or mice treated with irradiated (5000 rads) B16F1 melanoma cells. The animals also survived longer (P < 0.05) than mice with melanoma treated with IL-2-secreting LM cells transfected with genomic DNA from MOPC-315 cells, a nonimmunologically cross-reactive murine tumor. As determined by the capacity of monoclonal antibodies to T-cell subsets to inhibit the antimelanoma response in a 51Cr release assay, the antimelanoma immunity in mice immunized with cells transfected with genomic DNA from either B16F1 or B16F10 cells was mediated primarily by Lyt-2.2+ T-cells. These data raise the possibility that a generic, live cell tumor vaccine can be developed that can be modified to provide specificity for the neoplasms of individual patients.
Kim
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Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago 60612.
Cohen
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D004273:DNA, Neoplasm; D004351:Drug Resistance / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism / Q000637:transplantation*; D007114:Immunization / Q000379:methods; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008546:Melanoma, Experimental / Q000235:genetics / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D004273:DNA, Neoplasm; D007376:Interleukin-2