Monoclonal antibody therapy of spontaneous AKR T-cell leukemia

Abstract

We have previously shown that monoclonal antibodies against the Thy 1.1 differentiation antigen can inhibit the outgrowth of a lethal inoculum of transplanted AKR T-leukemic cells. In the present report we have extended these studies to examine antibody therapy of aged AKR/J mice with spontaneous leukemia. Infusion of anti-Thy 1.1 antibody in frankly leukemic mice led to uniform early mortality from cell lysis and agglutination. In contrast, anti-Thy 1.1 antibody therapy of mice in remission following treatment with cyclophosphamide prolonged remission duration (P less than 0.001) and modestly prolonged survival (P less than 0.01) compared to treatment with irrelevant antibody or chemotherapy alone. The major cause of failure was relapse of leukemia. In 85% (47 of 55) of cases relapse was due to cells that continued to express Thy 1.1, but in 15% of these relapsing animals all leukemic cells failed to express the target antigen. Our results suggest that monoclonal antibody against a normal T-cell antigen can add to the antileukemic effects obtained with chemotherapy alone. Nevertheless, the clinical benefit of unmodified antibody was modest, and antibodies conjugated to cytotoxic agents may be needed to overcome the limitations of unmodified antibodies.