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Cytomegalovirus tegument protein pp65, also known as the 65 kDa phosphoprotein or ppUL83, is a major structural component of the human cytomegalovirus (HCMV) virion [19]. While primarily known for its role in viral assembly and immune evasion during infection, pp65 has emerged as a significant therapeutic target in oncology due to its high expression in certain malignancies, particularly glioblastoma multiforme (GBM), while remaining absent in healthy brain tissue [1, 7, 10]. This tumor-specific expression allows pp65 to function as a neoantigen-like target for various immunotherapeutic strategies, including dendritic cell vaccines, peptide-based vaccines, and adoptive T-cell transfers [1, 2, 11]. In clinical settings, these therapies aim to stimulate a robust, antigen-specific cytotoxic T-lymphocyte response to selectively eliminate tumor cells [2, 10]. Research indicates that targeting pp65 can enhance the efficacy of standard treatments like temozolomide and radiation, potentially improving overall survival in patients with aggressive brain tumors [1, 6, 9].
Immunotherapy involving the induction of antigen-specific cellular immune responses, primarily through the activation of CD8+ and CD4+ T cells that recognize pp65 peptides presented on MHC molecules of tumor cells, leading to targeted cell lysis [1, 2, 10].
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