SPECIFICITY AND LONGEVITY OF ANTITUMOR IMMUNE-RESPONSES INDUCED BY B7-TRANSFECTED TUMORS

We have shown previously that expression of the costimulatory ligand B 7.1 by the UV-induced melanoma K1735 lends to rejection of the tumor b y syngeneic hosts and the induction of immunity to challenge by the pa rental B7-negative tumor. Here we extend our analysis of the effective ness 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 cel ls but is effective against an additional melanoma line and an unrelat ed fibrosarcoma as well, This immunity is, however, relatively short-l ived, and no significant protection is observed after 90 days, Depleti on of CD4+ T cells prior to rechallenge has no significant effect on t he subsequent rejection of B7-negative tumor cells. EL-4 thymoma cells transfected with B7.1 are also effectively rejected, and mice which h ave 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 shor t-lived immunity observed in the melanoma model, mice are effectively protected against challenge with EL-4 for longer than 90 days after re jection of B7 + EL-4. Finally, we show that irradiation severely dimin ishes the effectiveness of B7-positive tumor cells as immunogens. This work has implications for the use of B7-positive cells as tumor vacci nes.