MHC class II-transfected tumor cells induce long-term tumor-specific immunity in autologous mice.
Many tumors express peptides that are potentially immunogenic; however, the host's immune system is often not sufficiently stimulated to mediate tumor rejection. The inability to mount a potent antitumor immune response has often been attributed to the lack of generation of sufficient tumor-specific T cell help. Efforts in this laboratory to improve tumor-specific immunity have therefore focused on improving the generation of tumor-reactive T helper cells. Previous studies have suggested that immunity to the murine SaI sarcoma can be significantly improved if the tumor is engineered to express syngeneic MHC class II molecules, and thereby directly present tumor peptides to Th lymphocytes. In the present study we demonstrate that vaccination with class II+ SaI transfectants results in immunity that is extremely effective against high-dose challenges of wild-type SaI tumor. The immunity induced by immunization with these transfectants is also exceptionally long-lived (greater than 6 months) and radiation resistant, suggesting that tumor-specific memory T cells are generated. The resulting immunity is specific for the immunizing tumor and protects autologous mice against challenges of both ascites and solid SaI variants. Depletion and adoptive transfer studies confirm the role of CD4+ T cells in the induced immunity, supporting the hypothesis that improving the generation of Th cells enhances the antitumor immune response. Inasmuch as irradiated or paraformaldehyde-fixed transfectants are as effective as live transfectants in stimulating tumor rejection, these genetically engineered tumor cells may serve as useful vaccines against wild-type neoplasms.
Baskar
S
S
Department of Biological Sciences, University of Maryland, Baltimore 21228.
Azarenko
V
V
Garcia Marshall
E
E
Hughes
E
E
Ostrand-Rosenberg
S
S
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D005260:Female; D005720:Gamma Rays; D005802:Genes, MHC Class II / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D007111:Immunity, Cellular / Q000528:radiation effects; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008297:Male; D051379:Mice; D012513:Sarcoma, Experimental / Q000276:immunology / Q000517:prevention & control*; D014162:Transfection; D014182:Transplantation, Autologous
D000945:Antigens, Differentiation, T-Lymphocyte; D000949:Histocompatibility Antigens Class II