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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。卵巢癌是免疫原性的，与肿瘤诱导的免疫抑制的多种机制有关。最近的研究发现了一种独特的CD4+CD25+ T调节细胞（Tregs）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方面发挥作用。最近的研究表明，肿瘤间T细胞与卵巢癌患者预后的改善以及化疗反应的改善有关。对晚期卵巢癌患者的研究表明，腹膜肿瘤相关淋巴细胞中Tregs增加。Tregs可能抑制腹膜诱导主动免疫的企图，因此，腹膜相关Tregs的消耗可能提供一种恢复或诱导抗肿瘤免疫的方法。临床研究表明，ONTAK在治疗表达CD25的恶性肿瘤中是一种安全有效的药物。在这项I期研究中，我们将(1)评估ipp给药ONTAK的安全性，(2)确定ipp的最大耐受剂量，(3)收集ipp ONTAK对外周血和腹膜Tregs的影响数据。

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.