Expression of activated H-rasval12 in nontumorigenic and non-cross-reactive syngeneic cells induces tumor antigens cross-reactive with rat mammary adenocarcinoma 13762.
Adenocarcinoma 13762 expresses tumor Ags that can induce protective immunity to tumorigenic challenge. Syngeneic fibroblast Rat1 cells transformed by expression of H-rasval12 (Rat1/ras) but not parental Rat1 cells, and p53-transformed Rat1 cells, or other syngeneic cells or tumors, can immunize rats against tumorigenic challenge of 13762 tumor. Coincident with induced resistance to 13762 tumors, immunization of rats with Rat1/ras tumor induces CD4+ T cells that cross-react with adenocarcinoma 13762 in vitro and transfer protective immunity to tumorigenic 13762 challenge in vivo. Cross-reactive tumor Ags expressed in Rat1/ras tumor are not derived from ras protein, because immunization with purified H-rasval12 protein induces protective immunity to challenge by Rat1/ras tumor but not to adenocarcinoma 13762. In addition, immunization with H-rasval12 protein induces anti-ras CD4+ T cells that are uniquely reactive with Rat1/ras tumor: anti-ras T cells are not reactive with 13762 tumor in vitro and do not confer protective immunity to challenge with 13762 tumor in vivo. Tumor Ags expressed in Ras-transformed Rat1 cells that elicit cross-protective immunity likely arise as a consequence of transformation mediated by activated ras oncogene but are not derived from the Ras protein sequence.
Frey
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AB
Department of Cell Biology, New York University Medical Center, NY 10016, USA.
Cestari
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S
D000230:Adenocarcinoma / Q000276:immunology; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D005260:Female; D005347:Fibroblasts / Q000276:immunology; D007114:Immunization; D008325:Mammary Neoplasms, Experimental / Q000276:immunology; D051381:Rats; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000096:biosynthesis* / Q000276:immunology
D000951:Antigens, Neoplasm; D018631:ras Proteins