Elimination of EL-4 and L1210 Murine Tumors by 1,3-bis (2-Chloroethyl)-1-Nitrosourea Requires an Intact Immune Response

Abstract

Abstract

The chemotherapeutic agent 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) is commonly used to treat several types of human cancers. Recent investigations have suggested that elimination of tumor by BCNU is dependent on more than the cytotoxic activity of the drug. We have extended those 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 intraperitoneal injection of BCNU. When CS, an inhibitor of the activation of T lymphocytes, was administered to mice that had received either EL-4 or L1210 tumor and were treated with BCNU, nearly all the mice died 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 therapy did not occur. Finally, the ability of animals that had been cured of tumor by the BCNU therapy to reject a lethal challenge dose of homologous tumor was shown to be CS insensitive. These results suggest that the BCNU-mediated elimination of tumor from mice requires a functional immune response in addition to the cytotoxic activity of this chemotherapeutic agent.