AUTOLOGOUS THERAPEUTIC TUMOR VACCINE + IFN GAMMA IN OVARIAN CANCER

自体治疗性肿瘤疫苗 IFN GAMMA 治疗卵巢癌

• 批准号: 6265671
• 负责人: RALPH Stuart FREEDMAN
• 金额: $ 1.11万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6265671
• 关键词: cell proliferation; clinical research; clinical trial phase I; combination cancer therapy; cytotoxic T lymphocyte; cytotoxicity; dendritic cells; drug administration rate /duration; drug screening /evaluation; histocompatibility antigens; human subject; human therapy evaluation; injection /infusion; interferon gamma; interleukin 12; leukocyte activation /transformation; neoplasm /cancer immunology; neoplasm /cancer immunotherapy; neoplasm /cancer vaccine; neoplastic cell; neoplastic process; ovary neoplasms; transforming growth factors; tumor infiltrating lymphocyte; vaccine development

The long-term goal of this study is to develop effective specific tumor immune therapy for ovarian cancer. Results from a number of preclinical studies suggest that it is possible to induce anti-tumor T-cell activation in vivo by the use of a therapeutic vaccine composed of autologous tumor cells that co-express MHC antigens and the B7.1 costimulatory factor. Results of previous studies suggest that ovarian tumor infiltrating lymphocytes may in some instances represent a population of lymphocytes that have been activated in vivo, and that the MHC is involved in the activation process. It is probable that dendritic cells or other professional APC's contribute to activation of T-cells in vivo. We have identified dendritic cells in the peritoneal cavity of EOC patients, but for the most part these cells do not express CD80. We have therefore proposed a pilot clinical trial to determine whether IP injection of freshly isolated EOC cells infected with the ALVAC-hB7.1 is feasible, and whether the IP injection of autologous tumor cells that also express B7.1 results in activation of tumor specific immunity in vivo by standard methods of evaluation. Patients will be treated at 3 dose levels of ALVAC-B7.1 infected cells. ALVAC-B7.1 infected tumor cells only will be given the first week. Two doses of rIFN-g will precede treatment with ALVAC-B7.1 infected tumor cells in weeks 2 and 3. The 3 week treatment equals a single course of treatment. In the absence of progression and if tumor cells are available, further courses of vaccine and rIFN will be administered.

这项研究的长期目标是开发针对卵巢癌的有效特异性肿瘤免疫疗法。大量临床前研究的结果表明，通过使用由共表达 MHC 抗原和 B7.1 共刺激因子的自体肿瘤细胞组成的治疗性疫苗，可以在体内诱导抗肿瘤 T 细胞激活。 先前的研究结果表明，卵巢肿瘤浸润淋巴细胞在某些情况下可能代表体内已激活的淋巴细胞群，并且 MHC 参与激活过程。 树突状细胞或其他专业 APC 可能有助于体内 T 细胞的激活。 我们已经在 EOC 患者的腹膜腔中发现了树突状细胞，但大多数情况下这些细胞不表达 CD80。 因此，我们提出了一项试点临床试验，以确定腹腔注射感染 ALVAC-hB7.1 的新鲜分离的 EOC 细胞是否可行，以及腹腔注射同样表达 B7.1 的自体肿瘤细胞是否会导致肿瘤特异性激活通过标准方法评估体内免疫力。患者将接受 3 个剂量水平的 ALVAC-B7.1 感染细胞治疗。仅在第一周给予 ALVAC-B7.1 感染的肿瘤细胞。 在第 2 周和第 3 周用 ALVAC-B7.1 感染的肿瘤细胞治疗之前，将使用两剂 rIFN-g。3 周的治疗相当于单个疗程。 在没有进展的情况下，如果有肿瘤细胞，将进行进一步的疫苗和 rIFN 疗程。