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Tumor-associated peptide–HLA class I complexes recognized by TVGN 960 CD8+ TCRs are the primary therapeutic targets for TVGN 960, an off-the-shelf, genetically unmodified cytotoxic T lymphocyte (CTL) therapy developed by Tevogen Bio (Tevogen Bio, 2024). These complexes consist of specific antigenic peptides, typically derived from Human Papillomavirus (HPV) oncoproteins such as E6 and E7, presented on the surface of malignant cells by Human Leukocyte Antigen (HLA) class I molecules (SEC.gov, 2024). TVGN 960 is specifically designed to treat HPV-related oropharyngeal (mouth and throat) cancers by leveraging naturally occurring CD8+ T cells that possess high-affinity T-cell receptors (TCRs) for these specific pHLA targets (GlobeNewswire, 2024). Upon recognition of the complex, the CTLs initiate a targeted immune response, releasing cytotoxic granules like perforin and granzymes to induce apoptosis in the cancer cells while sparing healthy tissue that lacks the specific viral-peptide presentation (Tevogen Bio, 2024). This approach aims to provide a precision immunotherapy option for patients with HPV-driven malignancies, particularly those who are HLA-matched to the therapeutic product (BioWorld, 2024). By utilizing naturally occurring TCRs rather than genetically engineered ones, the therapy seeks to maximize immunologic specificity and safety (SEC.gov, 2024).
T-cell receptor (TCR) mediated recognition of peptide-HLA complexes leading to cytotoxic T-lymphocyte (CTL) activation and tumor cell lysis.
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