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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。卵巢癌具有免疫原性，并与多种肿瘤诱导的免疫抑制机制相关。最近的研究已经确定了一个独特的CD 4 + CD 25 + T调节细胞（T细胞）群体，其功能是“专业”抑制细胞，可能在防止卵巢肿瘤被免疫系统识别中发挥作用。最近的研究表明，肿瘤间T细胞与卵巢癌患者改善的结果以及改善的化疗反应有关。在晚期卵巢癌患者中的研究已经证明腹膜肿瘤相关淋巴细胞中的TdR增加。胸腺肽可以抑制诱导腹膜中主动免疫的尝试，因此，腹膜相关胸腺肽的消耗可以提供恢复或诱导抗肿瘤免疫的方式。临床研究表明，ONTAK是一种安全有效的治疗表达CD 25的恶性肿瘤的药物。在这项I期研究中，我们将（1）评价ONTAK腹腔内给药的安全性，（2）确定腹腔内最大耐受剂量，（3）收集ONTAK腹腔内给药对外周血和腹膜中TdR影响的数据。

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.