Antigenicity of L1210 leukemic sublines induced by drugs.

Abstract

Summary Thirty sublines of leukemia L1210 partially or completely drug resistant, originating after prolonged treatment in vivo with different anticancer agents, were found to have developed greater antigenicity than the original drug-sensitive line. The studies demonstrated increased survival time for mice given injections of the resistant sublines, as compared with the parent sensitive leukemia, and an increased response to treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea. The increases in survival time in untreated and treated mice inoculated with the drug-resistant sublines were reversed when mice were previously immunosuppressed. Animals immunized with inactivated cells from two of these resistant sublines were markedly protected against a challenge of viable leukemic cells from the same subline used for immunization. For mice immunized with inactivated sensitive cells, protection was considerably less extensive. Specific cytotoxic antibodies were demonstrated in sera of mice immunized with cells of a resistant subline. Cytotoxicity could not be demonstrated with antisera to sensitive L1210. The data support the hypothesis that new antigen(s) have been produced in drug-resistant variants of leukemia L1210.