An optimum anti-melanoma response in mice immunized with fibroblasts transfected with DNA from mouse melanoma cells requires the expression of both syngeneic and allogeneic MHC-determinants.
Most neoplasms do not induce antitumor immune responses that can control tumor growth. Tumor associated antigens (TAAs) are insufficiently immunogenic. A vaccine that augments the immunogenic properties of TAAs could be of importance in the treatment of cancer patients. In an animal model, we prepared a vaccine by transfection of highly antigenic allogeneic mouse fibroblasts (LM; H-2(k)) with DNA from B16 mouse melanoma cells. We then tested the transfected cells' immunogenic properties in C57BL/6 mice, syngeneic with the melanoma (H-2(b)). We hypothesized that the immunogenic properties of 'weak' TAAs formed by the neoplasm would be enhanced if they were expressed by highly antigenic cells. The results indicated that mice with melanoma treated by immunization with the DNA-transfected fibroblasts survived significantly longer than mice in various control groups. To investigate the contribution of MHC determinants expressed by the transfected cells to their immunogenic properties, we compared the antimelanoma responses in mice immunized with transfected cells that expressed allogeneic or syngeneic class I determinants. The results indicated that the immunogenic properties of the DNA-transfected cells were enhanced if the cells expressed allogeneic MHC determinants. The antimelanoma responses of greatest magnitude, however, mediated predominantly by CD8(+) T cells, were in mice immunized with transfected fibroblasts that expressed both syngeneic and allogeneic class I determinants.
de Zoeten
E F
EF
Department of Microbiology and Immunology, University of Illinois at Chicago, IL 60612, USA.
Markovic
D
D
Cohen
E P
EP
D000818:Animals; D002460:Cell Line; D004273:DNA, Neoplasm / Q000008:administration & dosage* / Q000235:genetics; D000939:Epitopes / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000276:immunology*; D015316:Genetic Therapy / Q000379:methods*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods*; D008546:Melanoma, Experimental / Q000628:therapy*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D014162:Transfection
D004273:DNA, Neoplasm; D000939:Epitopes; D015395:Histocompatibility Antigens Class I