Defining the T-cell Response to Human Renal Cancer

定义 T 细胞对人类肾癌的反应

• 批准号: 7331264
• 负责人: James C Yang
• 金额: --
• 依托单位: DIVISION OF CLINICAL SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7331264
• 关键词: Defining; cell; Response; Human; Renal

Our laboratory is elucidating the nature of the immune response to tumors and establishing principles which may enhance our ability to immunize patients against known tumor antigens and induce tumor regression with cytokine therapy. We have developed methodologies for identifying tumor-specific CTL from patients with renal cell cancer and successfully used these techniques to identify unmutated FGF-5 as an HLA-A3 restricted antigen on RCC, recognized by T-cells. There is now an active clinical protocol immunizing patients with RCC with peptides from FGF-5. Continuing these efforts looking at other antigens expressed on RCC, we have found tumor-reactive T-cells in patients with RCC which recognize their own tumors as well as allogeneic RCCs. Some of these cells have unusual reactivity profiles and novel recognition mechanisms tumors. We are studying a CD4 clone that recognizes nearly all RCC regardless of classical MHC type yet utilizes the T-cell receptor. This class of T-cells could be a valuable reagent for addressing tumors which have lost MHC expression. Finally, we have also activated a protocol in which patients will be treated with their RCC-reactive T-cells discovered through these efforts.

我们的实验室正在阐明对肿瘤的免疫反应的性质，并建立可能增强我们免疫患者免受已知肿瘤抗原的能力并通过细胞因子治疗诱导肿瘤退化的能力。我们已经开发了从肾脏细胞癌患者中鉴定出肿瘤特异性CTL的方法，并成功地使用了这些技术鉴定未经物质的FGF-5作为T细胞识别的RCC上的HLA-A3限制抗原。现在有一种活跃的临床方案，可以通过FGF-5的肽免疫RCC患者。继续研究在RCC上表达的其他抗原的这些努力，我们发现RCC患者肿瘤反应性T细胞识别自己的肿瘤以及同种异体RCC。这些细胞中的一些具有异常的反应性谱和新型识别机制肿瘤。我们正在研究一个CD4克隆，该克隆几乎识别所有RCC，而不论经典MHC类型如何，但使用T细胞受体。这类T细胞可能是解决失去MHC表达的肿瘤的宝贵试剂。最后，我们还激活了一项方案，在该方案中，将使用通过这些努力发现的RCC反应性T细胞进行治疗。