Immunological resistance to L1210 leukemia induced by viable L1210/DTIC cells

Summary Permanent, drug-induced antigenic alterations, not detectable in parental cells and transmissible after the withdrawal of treatment with the drug, have been obtained in mouse lymphoma. Viable L1210/DTIC cells, because they are rejected by syngeneic animals and carry L1210-associated TAA, can elicit host resistance to a subsequent inoculum of parental L1210. Mice challenged with viable L1210/DTIC cells, following rejection, were more resistant than mice immunized with inactivated parental cells. Resistance was specific and related to the immunogenicity of the TAA of the original tumor line employed.Active immunization was potentiated by adoptive transfer of immune lymphocytes, as evidenced by marked improvement in animal survival. Also, the treatment of tumor-bearing animals with anticancer compounds in conjunction with immunological alteration may result in an improved therapeutic response. BCNU administered to immunized animals 6 days after challenge with parental tumor cells resulted in augmented host survival, possibly attributable to partial resistance of a secondary immune response to the drug and a late nadir of immunosuppression, occurring after the completion of therapeutic action. Cyclophosphamide given before immunization enhanced host survival to a subsequent challenge of L1210 leukemia, conceivably as the result of preferential inhibition of T suppressor cells.