Activation of multiple effector mechanisms to enhance tumor lmmunotherapy

Recent technical advances have enabled the generation of clinical reagents for immunotherapy. Currently, treatment protocols combining both interleukin-2 (IL-2) and tumor-specific monoclonal antibody are underway at the University of Wisconsin Comprehensive Cancer Center and elsewhere. These approaches are based on the hypothesis that IL-2-activated lymphocytes will use tumor-reactive antibody to more selectively and effectively destroy tumor in vivo. Just as IL-2 can activate lymphocytes to destroy antibody-coated tumor cells, other agents can activate neutrophils and monocytes to destroy antibody-treated tumor cells. We are investigating, in the laboratory and clinic, approaches aimed at eventually using combinations of distinct antibody- based tumor recognition mechanisms in patients whose monocytes, neutrophils, and lymphocytes have been simultaneously activated with multiple biologic agents.