Cytotoxic T Lymphocyte Immunotherapy for Ovarian Cancer

描述：(由申请人提供)本提案描述了I期临床 肿瘤抗原特异性细胞毒性T淋巴细胞(CTL)过继免疫试验 卵巢复发化疗耐药患者的免疫治疗 癌症。在这项试验中，受试者将接受白细胞分离以收集 前体淋巴细胞。然后这些前体细胞将被刺激并 在存在MUC1的情况下进行培养扩增，MUC1是一种特异性的粘蛋白抗原 几种恶性的人类细胞，包括卵巢癌。由此产生的CTL 然后通过腹膜内输注给受试者。它是 假设这些体外产生的肿瘤特异性CTL将克服 正常肿瘤诱导的宿主免疫抑制和启动有效的肿瘤细胞 杀戮，毒性最小。试验的具体目的是：1) 确定腹膜腔内输液的毒性和可行性 2)确定肿瘤特异性CTL的迁移模式/分布 用~(111)In放射性同位素标记CTL；3)测定 CTL生成和输注的重复周期逐渐增加 可测量的卵巢癌比活度；4)临床观察 接受MUC1特异性CTL治疗的患者的反应，如果可能，与 对迁移模式和卵巢癌特异性水平的反应 CTL生成的活动。这项试验的长期目标是服务于 作为更大范围测试这一治疗效果的基础 技术，并最终开发出一种新的卵巢治疗方法 可单独使用或与现有方法结合使用的癌症 改善结果。

DESCRIPTION: (Provided by applicant)This proposal describes a phase I clinical trial using tumor antigen specific cytotoxic T-lymphocytes (CTLs) as adoptive immunotherapy for patients with recurrent chemotherapy-resistant ovarian cancer. In this trial, subjects will undergo leukopheresis for collection of precursor lymphocytes. These precursor cells will then be stimulated and expanded in culture in the presence of MUC1, a mucin antigen specific to several malignant human cells, including ovarian cancer. The resulting CTLs will then be administered to the subject via intraperitoneal infusion. It is hypothesized that these ex-vivo generated, tumor-specific CTLs will overcome normal tumor-induced host immunosuppression and initiate effective tumor cell killing, with minimal toxicity. The specific aims of the trial are 1) to determine the toxicity and feasibility of the use of intraperitoneal infusions of tumor specific CTLs; 2) to determine the migration pattern/distribution of the CTLs by use of 111-Indium radioisotope labeling; 3) to determine if repetitive cycles of CTL generation and infusion progressively increase the measurable ovarian cancer specific activity; and 4) to observe clinical response of patients receiving MUC1-specific CTL, and if possible, correlate response to migration patterns and to the level of ovarian cancer specific activity generated by the CTLs. The longer-term goal of this trial is to serve as a basis for larger scale testing of the therapeutic effect of this technique, and ultimately to develop a new treatment modality for ovarian cancer that may be used alone or in combination with existing methods to improve outcome.