ELIMINATION OF EL-4 AND L1210 MURINE TUMORS BY 1,3-BIS (2-CHLOROETHYL)-1-NITROSOUREA REQUIRES AN INTACT IMMUNE-RESPONSE

The chemotherapeutic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) is commonly used to treat several types of human cancers. Recent inve stigations have suggested that elimination of tumor by BCNU is depende nt on more than the cytotoxic activity of the drug, We have extended t hose findings by showing that cyclosporin A (CS) can inhibit the BCNU- mediated rejection of EL-4 or L1210 tumors in mice, It was shown that mice could be cured of EL-4 or L1210 ascites tumors with a single intr aperitoneal injection of BCNU, When CS, an inhibitor of the activation of T lymphocytes, was administered to mice that had received either E L-4 or L1210 tumor and were treated with BCNU, nearly all the mice die d by Day 60, When CS was administered to BCNU-treated mice starting at 1, 2, or 3 weeks after tumor injection, inhibition of the BCNU therap y did not occur, Finally, the ability of animals that had been cured o f tumor by the BCNU therapy to reject a lethal challenge dose of homol ogous tumor was shown to be CS insensitive, These results suggest that the BCNU-mediated elimination of tumor from mice requires a functiona l immune response in addition to the cytotoxic activity of this chemot herapeutic agent.