Specificity, efficacy, and toxicity of radioimmunotherapy in erythroleukemic mice

Abstract

Radioimmunotherapy with 131I-labeled monoclonal immunoglobulins was studied using the Rauscher murine erythroleukemia. Tumor-specific monoclonal antibody, nonrelevant monoclonal antibody, F(ab')2 fragments, polyclonal gamma-globulin, and serum albumin were used as carriers of 131I. Therapeutic effects as measured by the reduction in splenomegaly were seen with all the radiolabeled proteins tested, but not with 131I-tyrosine. Dose-response curves showed that about 90% reduction in spleen size occurred at 80 muCi injected per animal, irrespective of whether specific or nonrelevant monoclonal antibody was used. Therapeutic efficacy was affected by the size of the 131I-carrier and could be correlated with half-life of carrier protein in vivo. As expected, increase in the serum concentration of circulating antigen decreased the targeting of the tumor-specific monoclonal antibody and also contributed to a shorter half-life for the tumor-specific monoclonal antibody in leukemic animals compared to uninfected controls. This study showed that there was no therapeutic advantage to the use of tumor-specific monoclonal antibody over nonrelevant immunoglobulin as a carrier for 131I in the treatment of murine erythroleukemia and that, although it was extremely effective, radioimmunotherapy with 131I was not specific in this system.