Targeting an anti-viral CD8+ T cell response to a growing tumor facilitates its rejection.
We demonstrate in a murine model that targeting an anti-viral T cell response to a growing tumor facilitates priming of a tumor-associated antigen (TAA)-specific, rejecting T cell response. Murine P815 mastocytoma cells grow aggressively in a syngeneic host. Transfected P815/S cells (expressing the hepatitis B surface antigen, HBsAg) also grow as subcutaneous tumors, but occasional 'spontaneous' rejections after transient growth are observed. Growth of P815/S tumors (but not of P815 tumors) is efficiently suppressed by a CD8+ cytotoxic T lymphocyte (CTL)-dependent immune mechanism in mice primed to HBsAg by DNA-immunization. In hosts immunized against HBsAg by DNA vaccination, HBsAg-specific CTL are generated. This specific CTL reactivity was targeted to s.c.-growing P815 tumors by intra tumor injections of either HBsAg-encoding plasmid DNA or viable P815/S cells; this treatment led to tumor rejection in 70-80% of the tumor-bearing animals. All rejecting animals showed a CD8+ CTL-dependent resistance to subsequent challenges by native, non-transfected P815 tumors. Targeting an established anti-viral ('strong') CTL response to a growing tumor hence is an efficient strategy to facilitate priming of a rejecting CTL response against ('weak') TAA in this system.
Böhm
W
W
Department of Medical and Microbiological Hygiene, University of Ulm, Germany.
Schirmbeck
R
R
Reimann
J
J
D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000032:analysis / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis / Q000276:immunology*; D004247:DNA / Q000032:analysis / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology*; D006514:Hepatitis B Surface Antigens / Q000032:analysis / Q000235:genetics / Q000276:immunology; D008297:Male; D012515:Mast-Cell Sarcoma / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D010957:Plasmids; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured
D015295:Antigens, Tumor-Associated, Carbohydrate; D016827:CD8 Antigens; D004273:DNA, Neoplasm; D006514:Hepatitis B Surface Antigens; D004247:DNA