MANIPULATION OF LYMPHOCYTE HOMEOSTASIS ENHANCING ANTI-TUMOR IMMUNITY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 具体目标 成功的基于T细胞的治疗依赖于足够数量的肿瘤反应性T细胞的适当激活和这些反应的长期产生，这是防止肿瘤复发所必需的。然而，细胞动态平衡机制通过平衡T细胞的生成、存活和死亡来密切控制T细胞的总体大小和多样性，从而确保T细胞的初始和激活的恒定数量。这项建议的假设是，取消一些有助于维持T细胞动态平衡的免疫学机制，将使我们能够在接种代表肿瘤抗原的多肽或蛋白(Tag)后增强肿瘤反应性T细胞的生成，从而产生有效和长期的抗肿瘤活性。具体目标是： 目的1研究破坏淋巴细胞内稳态对疫苗刺激的抗肿瘤T淋巴细胞的扩增功能和持久性的影响。 目的2是评估在既有抗肿瘤T细胞反应的背景下，修饰T细胞稳态加肽/蛋白疫苗是否会优先增强抗肿瘤T细胞活性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Specific Aims Successful T cell-based therapy treat cancer patients depends upon the appropriate activation of sufficient numbers of tumor-reactive T cells and the long-term generation of these responses, which is necessary to prevent tumor recurrences. However, the cell homeostatic mechanisms closely govern the overall size and diversity of the T cell repertoire by balancing the generation, survival and death of thereby ensuring a constant number of na¿ve and activated T cells. The hypothesis being tested in this proposal is that abrogating some of the immunological mechanism that help maintain T cell homeostasis will allow us to enhance the generation of tumor-reactive T cells following vaccination with peptides or proteins representing tumor antigens (TAg), resulting in effective and long-lived anti-tumor activity against. The specific aims are to: Aim 1 was to study the effect of disrupting lymphocyte homeostasis on the expansion function and persistent of vaccine-stimulated anti-tumor T lymphocytes. Aim 2 was to assess whether modifying T cell homeostasis plus peptide/protein vaccine will preferentially augment anti-tumor T cell activity specifically, in the context of pre-existing anti-tumor T cell responses.