Enhanced response to chemoimmunotherapy and immunoprophylaxis with the use of tumor-associated antigens with a lipophilic agent

Abstract

Treating iodoacetamide (IAD)-modified lymphoma cells with the lipophilic agent dimethyldioctadecylammonium bromide (DDA) increased their immunogenicity as evidenced by the increased capacity of syngeneic, vaccinated hosts to reject subsequent implants of the same lymphoma. Under conditions of suboptimal immunization to facilitate comparison, there were 61% survivors among mice challenged with tumor implants after immunization with modified cells and DDA compared to 20% survivors among those immunized in the absence of DDA. The enhanced immune response was dependent on DDA dosage and was most striking when DDA was directly complexed to the IAD-treated cells. DDA was also effective with solubilized tumor antigen and with lymphoma cells not pretreated with IAD, but the latter had to be heat killed to assure that they were nontumorigenic. In therapy experiments BALB/c mice bearing P1798 were treated with methotrexate followed by immunotherapy with IAD-P1798 alone or complexed to DDA. With two and three cycles of therapy, methotrexate alone yielded 5 and 13% survivors, while adding immunotherapy with the DDA complex gave survival rates of 63 and 71%. In the absence of DDA, chemoimmunotherapy with methotrexate and IAD-P1798 gave intermediate results. In the absence of antigen, DDA was ineffective in either immunoprophylaxis or therapy experiments.