PHASE I DOSE ESCALATION STUDY OF INTRAPERITONEAL (IP) ONTAK IN OVARIAN CANCER

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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. Recent investigations have demonstrated that intertumoral T cells are associated with both improved outcome as well as improved response to chemotherapy in ovarian cancer patients. Studies in late stage ovarian cancer patients have demonstrated increased Tregs in peritoneal tumor associated lymphocytes. Tregs may inhibit attempts to induce active immunity in the peritoneum, and, thus, depletion of peritoneal associated Tregs may provide a way of restoring or inducing anti-tumor immunity. Clinical studies have shown ONTAK to be a safe and effective agent in the treatment of malignancies which express CD25. 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.