PHASE I DOSE ESCALATION STUDY OF INTRAPERITONEAL ONTAK IN ADVANCED OVARIAN CANCE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ovarian cancer is immunogenic and associated with multiple mechanisms of tumor induced immunosuppression. Recent studies have identified a unique population of CD4+CD25+ T regulatory cells (Tregs) which function as "professional" suppressor cells and may play a role in preventing ovarian tumors from being recognized by the immune system. Studies in ovarian cancer patients have demonstrated increased Tregs in peritoneal ascites. Thus, Tregs may inhibit attempts to induce active immunity in the peritoneum. Recent investigations have demonstrated that intratumoral T cells are associated with both improved outcome as well as improved response to chemotherapy in ovarian cancer patients. It is hypothesized that depletion of Tregs at the tumor site (peritoneum) by I.P. administration of ONTAK, a ligand fusion protein targeting diptheria toxin to CD25+ malignancies, may induce anti-tumor immunity by augmenting anti-tumor effectors including CD4+ T cells, CD8+ T cells, and functional intratumoral T cells. In this phase I study we will (1) evaluate the safety of I.P. administration of ONTAK, (2) establish the I.P. maximum tolerated dose, and (3) gather data on the effect of I.P. ONTAK on Tregs in peripheral blood and peritoneum.