Etoposide induction of tumor immunity in Lewis lung cancer

Abstract.

Purpose: To determine if the antineoplastic effect of etoposide includes alteration in Lewis lung cancer cells which evoke an immunologic response in C57B1/6 host mice. Methods and results: Of C57Bl/6 mice injected with 10⁶ 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 untreated 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 alterations in 3LL cells, which induce host immunity, leading to tumor rejection, C57Bl/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 harvested from tumor-rejecting mice protected naive mice injected with 3LL. Conclusion: These results support the hypothesis that in addition to its antineoplastic cytotoxic effect, VP-16 induces changes in 3LL cells which are recognized by the host immune system resulting in immune rejection of 3LL.