Large Molecule Therapeutics Antibody-Based Delivery of IL2 and Cytotoxics Eradicates Tumors in Immunocompetent Mice

Antibody–drug conjugates are increasingly being used for cancer therapy, but little is known about their ability to promote anticancer immunity, which may lead to long-lasting remissions. We investigated the therapeutic effect of antibody-based pharmacodelivery of cemadotin, a cytotoxic drug, and IL2, a strong proinflammatory cytokine. Using the F8 antibody, which selectively localizes to the tumor neovasculature, combination treatment led to tumor eradication, in a process dependent onCD8þT cells and natural killer cells in the C1498 syngeneic mouse model of acute myelogenous leukemia. The clinical combination of antibody– drug conjugates and antibody–cytokine proteins should be facilitated by their orthogonal toxicity profiles.Mol Cancer Ther; 13(7); 1772–6. 2014 AACR