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Human Papillomavirus (HPV) E6 and E7 oncoproteins are the primary drivers of cellular transformation and malignancy in HPV-associated cancers, including cervical, anal, and oropharyngeal carcinomas (NIH, 2023). These viral proteins promote oncogenesis by inactivating key tumor suppressor proteins, specifically p53 and the retinoblastoma protein (pRb), which leads to cell cycle deregulation and the inhibition of apoptosis (PubMed, 2022). When these antigens are expressed using a Modified Vaccinia Ankara (MVA) vector, they serve as the focal point for therapeutic vaccination strategies designed to elicit a robust cellular immune response. The MVA vector is a highly attenuated, non-replicating poxvirus that efficiently delivers the E6 and E7 genetic material into host cells, facilitating the endogenous production and presentation of these antigens to the immune system (Transgene, 2024). This process is intended to overcome the immune tolerance often observed in chronic HPV infections and established tumors by activating antigen-specific CD8+ cytotoxic T-lymphocytes. Consequently, the immune system is primed to identify and destroy cells that constitutively express these oncoproteins, providing a targeted approach to treating HPV-related pre-malignant lesions and invasive cancers (PubMed, 2021).
The MVA vector delivers genetic sequences of HPV E6 and E7 into host cells, leading to the expression and presentation of these antigens via MHC molecules to stimulate a systemic, antigen-specific CD8+ and CD4+ T-cell immune response (PubMed, 2021).
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