Specificity and longevity of antitumor immune responses induced by B7-transfected tumors.
We have shown previously that expression of the costimulatory ligand B7.1 by the UV-induced melanoma K1735 leads to rejection of the tumor by syngeneic hosts and the induction of immunity to challenge by the parental B7-negative tumor. Here we extend our analysis of the effectiveness of B7-positive tumor cells as vaccines to additional tumor models and analyze the protective immunity in detail. We have found that the immunity induced by K1735 is not restricted to the parental tumor cells but is effective against an additional melanoma line and an unrelated fibrosarcoma as well. This immunity is, however, relatively short-lived, and no significant protection is observed after 90 days. Depletion of CD4+ T cells prior to rechallenge has no significant effect on the subsequent rejection of B7-negative tumor cells. EL-4 thymoma cells transfected with B7.1 are also effectively rejected, and mice which have rejected B7 + EL-4 cells are immune to challenge with not only EL-4, but also reject an unrelated thymoma, C6VL. In contrast to the short-lived immunity observed in the melanoma model, mice are effectively protected against challenge with EL-4 for longer than 90 days after rejection of B7 + EL-4. Finally, we show that irradiation severely diminishes the effectiveness of B7-positive tumor cells as immunogens. This work has implications for the use of B7-positive cells as tumor vaccines.
Townsend
S E
SE
Cancer Research Laboratory, University of California at Berkeley 94720.
Su
F W
FW
Atherton
J M
JM
Allison
J P
JP
D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology* / Q000528:radiation effects; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000628:therapy; D015179:Colorectal Neoplasms / Q000276:immunology; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology* / Q000628:therapy; D006084:Graft Rejection / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000276:immunology; D012515:Mast-Cell Sarcoma / Q000276:immunology; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D009368:Neoplasm Transplantation / Q000276:immunology; D013945:Thymoma / Q000276:immunology* / Q000628:therapy
D018122:B7-1 Antigen; D000949:Histocompatibility Antigens Class II