CELL MEDIATED IMMUNITY TO OCULAR TUMORS

细胞介导的眼肿瘤免疫

• 批准号: 6138159
• 负责人: Bruce R Ksander
• 金额: $ 29.39万
• 依托单位: SCHEPENS EYE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6138159
• 关键词: cancer prevention; cell differentiation; cell mediated lymphocytolysis test; cellular immunity; cellular oncology; clinical research; cytotoxic T lymphocyte; eye neoplasms; gene therapy; helper T lymphocyte; human subject; interleukin 12; leukocyte activation /transformation; melanoma; metastasis; neoplasm /cancer immunology; neoplasm /cancer immunotherapy; neoplasm /cancer vaccine; northern blottings; polymerase chain reaction; tissue /cell culture; tumor antigens; tumor infiltrating lymphocyte; vaccine development

DESCRIPTION: Melanomas that develop within the eye are treated by a variety of different methods that, in general, successfully control primary tumor growth. However, all of these treatments fail to alter the incidence of metastatic disease, which is unusually high and occurs in approximately 50% of patients with medium to large tumors. Although there is a long delay between the appearance of primary tumors and the development of secondary tumors, once metastatic tumors are clinically detectable, they grow rapidly, are resistant to conventional forms of therapy, and are universally fatal. There is currently no successful treatment available for patients with metastatic melanomas derived from ocular tumors. Previous studies indicate that ocular melanomas are immunogenic tumors that express tumor antigens recognized by specific T cells. Tumor-specific lymphocytes are present within the patient s peripheral blood and among tumor-infiltrating-lymphocytes. In order to successfully activate specific T cells, the PI proposes to use a form of gene therapy that increases the immunogenicity of primary ocular melanoma cells. The ultimate goal of this research is to develop a tumor cell vaccine that protects ocular melanoma patients from developing metastatic tumors. Protection is achieved by using primary tumor cells to stimulate tumor-specific T cells that eliminate metastatic tumor cells. He hypothesizes that primary tumor cells genetically engineered to express the costimulatory molecules B7.1 and interleukin-12 will stimulate tumor-specific cytotoxic T cells among the patient's peripheral blood lymphocytes. These lymphocytes will possess the ability to eliminate metastatic tumor cells. The first specific aim will determine if primary tumor cells that express costimulatory signals (B7.1 and/or interleukin-12) induce proliferation of autologous T cells. The second specific aim will determine if tumor-specific cytotoxic T cells are present among these proliferating cells, and the third specific aim will determine if these cytotoxic T cells lyse metastatic tumor cells.

描述：眼睛内发育的黑色素瘤被多种 通常，多种方法成功控制原发性肿瘤 生长。 但是，所有这些治疗方法都无法改变 转移性疾病异常高，发生在大约50％ 中等至大肿瘤的患者。 虽然有很长的延迟 在原发性肿瘤的出现与次要的发展之间 肿瘤，一旦转移性肿瘤在临床上可检测到，它们就会迅速生长， 对常规的治疗形式有抵抗力，并且是普遍致命的。 目前尚无针对患者的成功治疗 来自眼部肿瘤的转移性黑色素瘤。 先前的研究表明，眼黑色素瘤是免疫原性肿瘤 特异性T细胞识别的表达肿瘤抗原。 肿瘤特异性 淋巴细胞存在于患者的外周血中， 肿瘤浸润细胞。 为了成功激活特定 T细胞，PI建议使用一种基因治疗形式，以增加 原代眼黑色素瘤细胞的免疫原性。 这项研究的最终目的是开发一种肿瘤细胞疫苗 保护眼部黑色素瘤患者免受转移性肿瘤的发展。 通过使用原发性肿瘤细胞刺激来实现保护 消除转移性肿瘤细胞的肿瘤特异性T细胞。 他 假设原发性肿瘤细胞在基因上设计以表达 共刺激分子B7.1和白介素12将刺激 患者外周血中的肿瘤特异性细胞毒性T细胞 淋巴细胞。 这些淋巴细胞将具有消除的能力 转移性肿瘤细胞。 第一个特定目标将确定表达的原发性肿瘤细胞是否 共刺激信号（B7.1和/或白介素12）诱导 自体T细胞。 第二个特定目标将确定是否 在这些增殖中存在肿瘤特异性的细胞毒性T细胞 细胞，第三个特定目标将确定这些细胞毒性T细胞是否是否 裂解转移性肿瘤细胞。