Neoantigen-specific T-cell receptor recognizing POLE P286R peptide presented by HLA-A*11:01 (POLE-P286R-A1101-TCR)

The Neoantigen-specific T-cell receptor recognizing POLE P286R peptide presented by HLA-A*11:01 is a specialized immune receptor utilized in the development of TCR-engineered T-cell (TCR-T) therapies. It targets a highly immunogenic neoantigen derived from a recurrent hotspot mutation (P286R) in the exonuclease domain of DNA polymerase epsilon (POLE), which is a hallmark of ultramutated colorectal and endometrial carcinomas (Nature Genetics, 2014). This TCR is restricted to the HLA-A*11:01 MHC class I allele, ensuring that it only recognizes the mutated peptide when presented by this specific genetic background (Journal of Experimental Medicine, 2021). In a therapeutic setting, a patient's T cells are genetically modified to express this TCR, enabling them to selectively identify and eliminate tumor cells while sparing healthy tissues that lack the somatic mutation. This approach represents a precision immunotherapy strategy tailored for patients with POLE-deficient malignancies. Clinical efficacy depends on the dual presence of the POLE P286R mutation and the HLA-A*11:01 allele in the patient.

Other names

POLE P286R-specific T-cell receptorHLA-A*11:01 restricted POLE P286R TCRT-cell receptor recognizing POLE P286R/HLA-A*11:01 complexPOLE-mutant specific TCR

The TCR binds specifically to the POLE P286R mutated peptide presented by the HLA-A*11:01 MHC class I molecule on the surface of tumor cells. This binding event triggers the formation of an immunological synapse, leading to T-cell activation, the release of cytotoxic granules (perforin and granzymes), and the induction of apoptosis in the target cancer cell (Nature Reviews Cancer, 2021).