Interleukin-2-secreting mouse fibroblasts transfected with genomic DNA from murine neoplasms induce tumor-specific immune responses that prolong the lives of tumor-bearing mice.
Genetic alterations are a common feature of the malignant phenotype. Among other properties, altered genes may be responsible for invasion and metastasis, as well as for resistance to chemotherapeutic agents. Under appropriate circumstances, the products of other altered genes expressed by malignant cells may act as tumor-associated T-cell epitopes, capable of provoking antitumor immune responses. As a novel means of augmenting the immunogenicity of the gene products, unfractionated, sheared genomic DNA from various tumor cell lines (B16F1 melanoma, B16F10 melanoma, MOPC-315 plasmacytoma, C1498 lymphoma, or J558 myeloma), or from non-neoplastic liver cells of tumor-free mice, was transfected into LM cells, a mouse fibroblast cell-line (H-2k) that had been modified previously by retroviral gene transfer to secrete interleukin-2 (IL-2). The IL-2-secreting transfected cell populations were then tested for their immunogenic properties toward B16F1 (H-2b) or C1498 (H-2b) cells in syngeneic C57BL/6 mice. The antitumor responses were specific for the type of tumor from which the DNA was obtained. The survival of C57BL/6 mice injected with a mixture of viable B16F1 cells and IL-2-secreting LM cells transfected with DNA from B16F1 cells was significantly prolonged. In a similar manner, the survival of C57BL/6 mice injected with a mixture of C1498 cells and IL-2-secreting LM cells transfected with DNA from C1498 cells was prolonged as well. The immunity was mediated predominantly by CD8+ and natural killer/lymphokine-activated killer (NK/LAK) cells. These data raise the possibility that a cell line altered previously for cytokine secretion may be readily modified to provide immunologic specificity for the neoplasms of individual cancer patients.
Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago 60612-7344, USA.
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Sun
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Kim
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Waltz
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Cohen
D000818:Animals; D000941:Antigens / Q000378:metabolism; D016827:CD8 Antigens; D003602:Cytotoxicity, Immunologic; D004273:DNA, Neoplasm; D018984:Epitopes, T-Lymphocyte; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D007114:Immunization; D007376:Interleukin-2 / Q000378:metabolism*; D015979:Killer Cells, Lymphokine-Activated; D007694:Killer Cells, Natural; D008223:Lymphoma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008545:Melanoma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D015996:Survival Rate; D014162:Transfection; D014407:Tumor Cells, Cultured
D000941:Antigens; D016827:CD8 Antigens; D004273:DNA, Neoplasm; D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2