Immunization with interleukin-2-secreting allogeneic cells transfected with DNA from mouse melanoma cells induces immune responses that prolong the lives of mice with melanoma.
Altered genes in tumor cells specify tumor-associated antigens. Because genetic instability is a characteristic of the malignant cell phenotype, a large number of different, altered genes may be present in a population of neoplastic cells, specifying an array of undefined tumor-associated determinants. We hypothesized that immunogenic cells transfected with DNA from malignant cells will include cells that specify tumor-associated antigens. To test this question, we deliberately mutagenized a population of B16 melanoma cells (H-2b) by ultraviolet-B irradiation. DNA from the surviving cells was used to transfect LM cells (H-2k), a mouse fibroblast cell line modified previously to secrete interleukin-2. The transfected allogeneic cells were then tested for their immunogenic properties in C57BL/6J mice (H-2b) syngeneic with the melanoma. Mice injected with a mixture of the mutagenized B16 cells and the transfected cells survived significantly longer than untreated mice injected with the mutagenized B16 cells alone. Mice injected with a mixture of mutagenized B16 cells and cells transfected with DNA from unirradiated B16 cells died in shorter intervals. Based on the results of cytotoxicity assays performed in vitro, the cellular immune responses of greatest magnitude were directed toward the type of cell from which the DNA was obtained.
Sun
T
T
Department of Microbiology and Immunology, University of Illinois College of Medicine, University of Illinois at Chicago, 60612, USA.
Carr-Brendel
V
V
De Zoeten
E F
EF
Cohen
E P
EP
D000818:Animals; D019496:Cancer Vaccines; D002460:Cell Line; D004273:DNA, Neoplasm / Q000008:administration & dosage*; D019008:Drug Resistance, Neoplasm / Q000528:radiation effects; D007376:Interleukin-2 / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010042:Ouabain / Q000494:pharmacology; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D019496:Cancer Vaccines; D004273:DNA, Neoplasm; D007376:Interleukin-2; D010042:Ouabain