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HLA-engineered HPV-specific rejuvenated cytotoxic T lymphocytes

Development stage
Preclinical
Lead developer
Juntendo University
Modality
CRISPR-Cas9 → CRISPR Systems → Programmable Nucleases → Gene Editing → Gene Therapies, TCR-Engineered T Cells → Engineered T Cells → Adoptive Cell Transfer → Cell Therapies, iPSCs → Pluripotent Stem Cells → Stem Cell Therapies → Cell Therapies
Administration
Intravenous
01

Overview

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.

Other names
HLA-engineered HPV-specific rejuvenated T cellsHLA-engineered HPV-rejTs
02

Targets

Human papillomavirus type 16 E6 epitope presented by HLA-A*2402

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