178P Comprehensive immunophenotype analysis in anti-PD-1 antibody sensitive and resistant syngeneic mouse model unravels perforin-expressing CD4+T cells dominant cytolytic activity

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second biopsy after one year, and nine high-risk patients had radical prostatectomy within two months of the second injection.Biopsies, prostatectomy, and blood samples were analyzed for immune cell changes and tumor-specific T cells.Results: No dose-limiting toxicities or severe adverse events occurred with either single or repeated doses.Immunobiological analysis showed a shift from an immunologically cold state in pre-treatment biopsies to a hot TME in radical prostatectomy and one-year biopsies, with a rise in CD8+ and CD4+ T cells (up to 2000 cells/mm 2 ).PD-1 and Granzyme B-expressing T cells increased, while regulatory T cells stayed unchanged.Peripheral blood analysis showed an increase in HLA-DR+ and Ki67+ CD8+ T cells within weeks of ORCA-010 injection.CD4+ and CD8+ T cells reactive to prostate antigens emerged post-treatment, declining after radical prostatectomy, supporting the anti-tumor nature of these cells.Conclusions: Intraprostatic administration of ORCA-010 in prostate cancer patients was safe and induced local and systemic anti-tumor immune responses.The increase in tumor-infiltrating and circulating prostate-specific T cells, along with stable regulatory T cells, indicates a favorable immune environment.These findings suggest that ORCA-010 can convert cold tumors into immunogenic ones, highlighting its promise for prostate cancer immunotherapy.Clinical trial identification: NCT04097002.

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