Etoposide induction of tumor immunity in Lewis lung cancer

Purpose: To determine if the antineoplastic effect of etoposide includes al teration in Lewis lung cancer cells which evoke an immunologic response in C57B1/6 host mice. Methods and results: Of C57B1/6 mice injected with 10(6) Lewis lung cancer (3LL) cells followed by treatment with a single 50 mg/kg dose of etoposide (VP-16), 60% survived over 60 days, in contrast to untre ated control mice which died within 30 days. Approximately 40% of surviving mice rejected a subsequent challenge with 3LL. Their splenocytes protected naive mice injected with 3LL. To test if VP-16 treatment produced alterati ons in 3LL cells, which induce host immunity. leading to tumor rejection, C 57B1/6 mice were injected with 3LL cells that had survived an 80-90% lethal concentration of VP-16 in vitro. These cells killed 75% of recipient mice but 60% of the surviving mice rejected challenge with 3LL. Splenocytes harv ested from tumor-rejecting mice protected naive mice injected with 3LL. Con clusion: These results support the hypothesis that in addition to its antin eoplastic cytotoxic effect, VP-16 induces changes in 3LL cells which are re cognized by the host immune system resulting in immune rejection of 3LL.