Augmentation of the Activity of an Immunotoxin, Anti-Tac(Fv)-PE40KDEL, in T Cell Lines Infected with Human T Cell Leukemia Virus Type-I

Abstract

Therapy with an immunotoxin, anti-Tac(Fv)-PE38, which is a conjugate of the variable domains of an anti-Tac monoclonal antibody and Pseudomonas exotoxin, was reported to be useful for adult T cell leukemia (ATL) patients but a considerable amount of the immunotoxin is needed for the therapy and some side effects were also observed. We have previously demonstrated that an immunotoxin, anti-Tac(Fv)-PE40KDEL, showed strong cytotoxic effects on malignant cells from ATL patients. Therefore, we searched for agents that enhance the effects of the immunotoxin. PAK-200, FK-506, quinidine, cepharanthine and cyclosporine A (CsA) augmented the ability of the immunotoxin to inhibit protein synthesis in two human T cell leukemia virus type-I infected T cell lines, KUT-1 and KUT-2. CsA was the most potent agent in both the cell lines. Augmentation of the cytotoxic effect of the immunotoxin by these agents, especially CsA, may be useful in the immunotoxin therapy of ATL.