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HLA-engineered HPV-specific rejuvenated cytotoxic T lymphocytes (HLA-engineered HPV-rejTs) are an experimental 'off-the-shelf' cell therapy developed for the treatment of cervical cancer. The therapy utilizes induced pluripotent stem cells (iPSCs) derived from an HPV-specific cytotoxic T lymphocyte clone. These cells undergo a two-step CRISPR-Cas9 gene editing process: first, the deletion of all HLA class I antigens to prevent rejection by host CD8+ T cells, and second, the introduction of limited expression of HLA-A24 and HLA-E to evade natural killer (NK) cell-mediated lysis. The resulting rejuvenated T cells (rejTs) are enriched with tissue-resident memory T cell markers and target HPV-specific antigens predominantly expressed in cervical cancer cells. This approach aims to overcome the limitations of autologous T cell therapies by providing a sustainable, mass-produced alternative that can persist in the host without being rejected.
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