Immune response to somatic cell hybrids between ultraviolet radiation-induced regressor and spontaneous progressor C3H mouse tumor cells.
We used somatic cell hybridization to determine whether the regressor phenotype exhibited by UV-induced murine tumors was dominant or recessive and whether this technique could confer immunogenic properties on nonimmunogenic syngeneic tumors. We transfected a highly antigenic UV-induced C3H mouse tumor cell line (UV-2240) with the plasmid pSV2-neo and selected G418-resistant clones. The resulting cell line was fused with a spontaneously transformed nonimmunogenic C3H progressor tumor cell line (SF-2T) that had been selected previously for resistance to 3.0 mM ouabain. These two cell lines were fused by a brief exposure to polyethylene glycol and heterokaryons isolated by growth in medium containing both G418 and ouabain. Hybrid cell lines established from individual colonies and from pools of colonies were tested for tumorigenicity in normal C3H and athymic nude mice. The results indicated that all the hybrid cell lines tested were highly antigenic in that they were completely rejected when transplanted into normal syngeneic mice but grew progressively in nude mice. Furthermore, immunization of C3H mice with the hybrid cell lines induced protective immunity against challenge with the immunizing tumor and generated cross-protective immunity against challenge with the regressor parental cell line but not against challenge with the progressor parental cell line. These results demonstrate that the regressor phenotype of the UV-2240 tumor is dominant in nature and that the immune response induced by somatic cell hybrids is uniquely directed against the dominant tumor-specific transplantation antigens expressed on the regressor tumor. This implies that introduction of tumor-specific transplantation antigens from an immunogenic tumor into a nonimmunogenic tumor, although sufficient to confer immunogenic properties to the hybrid, is insufficient to induce cross-protective transplantation immunity against the nonimmunogenic tumor.
Chen
P W
PW
Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Kaba
D S
DS
Ananthaswamy
H N
HN
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D003429:Cross Reactions; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology* / Q000473:pathology; D006084:Graft Rejection; D006649:Histocompatibility Antigens / Q000276:immunology*; D006824:Hybridization, Genetic; D007108:Immune Tolerance; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D009365:Neoplasm Regression, Spontaneous; D009368:Neoplasm Transplantation; D009381:Neoplasms, Radiation-Induced / Q000276:immunology*; D010641:Phenotype; D013047:Specific Pathogen-Free Organisms; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014181:Transplantation Immunology; D014407:Tumor Cells, Cultured / Q000276:immunology
D000951:Antigens, Neoplasm; D006649:Histocompatibility Antigens; C029237:tumor-associated transplantation antigen