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TCR-T cells (cryptic antigen-directed)
- Development stage
- Preclinical
- Lead developer
- Dana-Farber Cancer Institute
- Modality
- CRISPR-Cas9 → CRISPR Systems → Programmable Nucleases → Gene Editing → Gene Therapies, TCR-Engineered T Cells → Engineered T Cells → Adoptive Cell Transfer → Cell Therapies
- Administration
- Intravenous
01
Overview
TCR-T cells (cryptic antigen-directed) are an experimental adoptive cell therapy utilizing T cell receptors (TCRs) engineered to recognize non-canonical HLA-I bound peptides (ncHLAp) derived from the dark proteome. These cryptic antigens result from the aberrant translation of unannotated open reading frames (nuORFs) in cancer cells, such as pancreatic ductal adenocarcinoma (PDAC), but are not found in healthy tissues. The therapy involves identifying these cancer-restricted (CR) ncHLAp through proteogenomics and Ribo-seq, isolating specific TCRs from healthy donor PBMCs, and using CRISPR-based redirection to engineer T cells. Preclinical studies have demonstrated that these TCR-T cells can effectively recognize and kill PDAC organoids in vitro and in vivo, offering a potential strategy for treating low mutational burden cancers.
- Other names
- cryptic antigen-directed TCR engineered T cellsCR ncHLAp-directed TCR-T cells
02
Targets
pMHC-I (Peptide–MHC class I complex)
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