PRODUCTION AND IN-VIVO CHARACTERIZATION OF A BIFUNCTIONAL ANTIBODY (IVA039.1) WITH SPECIFICITY FOR THE MOUSE INTERLEUKIN-2 RECEPTOR AND VINCA ALKALOIDS

The autoreactive T cell plays a pivotal role in the pathogenesis of ty pe I diabetes in humans and in rodent animal models. Elimination or at tenuation of these cells may provide a means to treat the disease. The use of antibodies directed to T cells has shown varying degrees of ef fectiveness in the treatment of autoimmune disease. The use of a bifun ctional antibody directed to T cells with a cytolytic agent may provid e an additional level of therapeutic efficacy compared to anti-T-cell antibodies alone. To test this hypothesis, we prepared a bifunctional antibody (IVA039.1) with specificity for the mouse interleukin-2 (IL-2 ) receptor and vinca alkaloids. The antibody was derived from the fusi on of vinca immune spleen cells with PC61 5.3, a hybridoma that produc es rat anti-mouse IL-2 receptor antibody. IVA039.1 was purified by aff inity chromatography through Protein A and anti-vinca affinity columns followed by TSK-DEAE high-pressure liquid chromatography (HPLC). Bifu nctionality of the antibody was confirmed by fluorescence-activated ce ll sorting (FACS) analysis, enzyme-linked immunoadsorbent assay (ELISA ) and a cell assay designed to measure simultaneously both IL-2 recept or and vinca reactivities. The biodistribution of IVA039.1 was determi ned in normal and streptozotocin-complete Freund's adjuvant (CFA) indu ced diabetic mice. Enhanced uptake of IVA039.1 was observed in the pan creata, spleens, and lymph nodes of diabetic compared to normal mice. These data suggest that bifunctional antibodies that can deliver cytol ytic agents to T cells may be appropriate candidates for the treatment of diabetes and other autoimmune diseases.