THERAPY OF STREPTOZOTOCIN-INDUCED DIABETES WITH A BIFUNCTIONAL ANTIBODY THAT DELIVERS VINCA ALKALOIDS TO IL-2 RECEPTOR-POSITIVE CELLS

IVA039.1 is a bifunctional antibody with specificity for the murine IL -2 receptor and vinca alkaloids. Biodistribution studies show that IVA 039.1 can target end deliver vinca alkaloids to tissues that contain I L-2 receptor positive cells. Vinca alkaloids are lymphocytotoxic. Ther apy of diabetic mice with IVA039.1 plus vincristine results in a signi ficant decrease in the glucose levels of diabetic compared to untreate d mice. The therapeutic effect of IVA039.1 plus vincristine therapy wa s additive but surprisingly not synergistic. The binding of IVA039.1 t o vincristine has moderate affinity with a slow off rate. In vitro stu dies suggest that, when bound to IVA039.1, the vincristine is inactiva ted. We attribute the lack of an enhanced therapeutic response to bifu nctional antibody therapy using IVA039.1 plus vincristine to the inace ssibility of the drug to the target cells.