Cytotoxic T Lymphocyte Immunotherapy for Ovarian Cancer

卵巢癌的细胞毒性 T 淋巴细胞免疫疗法

• 批准号: 6401983
• 负责人: WILLIAM R ROBINSON
• 金额: $ 19.58万
• 依托单位: DON AND SYBIL HARRINGTON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-12 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6401983
• 关键词: clinical trial phase I; cytotoxic T lymphocyte; drug adverse effect; female; human subject; human therapy evaluation; indium; neoplasm /cancer immunology; neoplasm /cancer immunotherapy; neoplasm /cancer relapse /recurrence; ovary neoplasms; patient oriented research; tumor antigens; women's health

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.

描述：（由申请人提供）本提案描述了一项I期临床试验 使用肿瘤抗原特异性细胞毒性T淋巴细胞（CTL）作为过继性的试验 复发性化疗耐药卵巢癌患者免疫治疗 癌在本试验中，受试者将接受白细胞去除术， 前体淋巴细胞这些前体细胞将被刺激， 在MUC 1存在下在培养物中扩增，MUC 1是一种特异于 包括卵巢癌在内的几种恶性人类细胞。产生的CTL 然后通过腹膜内输注给予受试者。是 假设这些离体产生的肿瘤特异性CTL将克服 正常肿瘤诱导的宿主免疫抑制和启动有效肿瘤细胞 以最小的毒性杀死。审判的具体目的是：1） 确定使用腹腔内输注的毒性和可行性 2）确定肿瘤特异性CTL的迁移模式/分布 通过使用111-铟放射性同位素标记CTL; 3）确定是否 CTL产生和输注的重复循环逐渐增加了细胞的免疫应答。 可测量的卵巢癌特异性活性;和4）观察临床 接受MUC 1特异性CTL的患者的应答，如果可能， 对迁移模式和卵巢癌特异性 由CTL产生的活动。这项试验的长期目标是 作为更大规模测试这种治疗效果的基础， 技术，并最终开发一种新的治疗卵巢癌的方式， 可以单独使用或与现有方法组合使用， 改善结果。