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 IVA039.1 can target and deliver vinca alkaloids to tissues that contain IL-2 receptor positive cells. Vinca alkaloids are lymphocytotoxic. Therapy of diabetic mice with IVA039.1 plus vincristine results in a significant decrease in the glucose levels of diabetic compared to untreated mice. The therapeutic effect of IVA039.1 plus vincristine therapy was additive but surprisingly not synergistic. The binding of IVA039.1 to vincristine has moderate affinity with a slow off rate. In vitro studies suggest that, when bound to IVA039.1, the vincristine is inactivated. We attribute the lack of an enhanced therapeutic response to bifunctional antibody therapy using IVA039.1 plus vincristine to the inaccessibility of the drug to the target cells.
Kuus-Reichel
K
K
Hybritech Incorporated, San Diego, CA 92196-9006, USA.
Knott
C
C
Sam-Fong
P
P
Petrella
E
E
Corvalan
J R
JR
D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology* / Q000627:therapeutic use*; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced* / Q000628:therapy*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013311:Streptozocin / Q000633:toxicity*; D014748:Vinca Alkaloids / Q000276:immunology* / Q000627:therapeutic use*; D014750:Vincristine / Q000037:antagonists & inhibitors / Q000276:immunology / Q000627:therapeutic use
D018033:Antibodies, Bispecific; D015375:Receptors, Interleukin-2; D014748:Vinca Alkaloids; D014750:Vincristine; D013311:Streptozocin