MANIPULATION OF LYMPHOCYTE HOMEOSTASIS ENHANCING ANTI-TUMOR IMMUNITY

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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.