T-cell receptor recognizing LY6K-derived peptide–MHC complexes (LY6K-TCR)

The T-cell receptor (TCR) recognizing LY6K-derived peptide–MHC complexes is a specialized antigen receptor engineered or naturally occurring to target Lymphocyte Antigen 6 Family Member K (LY6K). LY6K is a cancer-testis antigen that is highly overexpressed in various solid tumors, including lung, esophageal, and gastric cancers, while its expression in normal tissues is restricted to the testis, making it an ideal target for immunotherapy (PubMed: 19459850, 34805015). These TCRs specifically bind to LY6K peptides, such as the HLA-A*24:02-restricted LY6K-177 (RYCNLEGPPI), presented on the surface of malignant cells (PubMed: 17906276). Upon binding, the TCR triggers T-cell activation, leading to the secretion of cytotoxic granules and cytokines that induce tumor cell apoptosis (PubMed: 24363238). Therapeutic strategies utilizing these TCRs primarily involve TCR-engineered T-cell (TCR-T) therapy, where a patient's T cells are modified to express the LY6K-specific receptor to enhance anti-tumor immunity (NIH: PMC11158753). Clinical trials have also explored peptide vaccines that induce these TCRs endogenously, demonstrating safety and potential efficacy in advanced cancer patients (ClinicalTrials.gov: NCT00682227). The development of these receptors represents a significant advancement in precision oncology, offering a way to target intracellular tumor antigens that are inaccessible to traditional antibody-based therapies (PubMed: 24155313).

Other names

LY6K-specific T-cell receptorLY6K-targeted TCRTCR recognizing LY6K/HLA-A*24:02TCR recognizing LY6K/HLA-A*02:01URLC10-specific T-cell receptor

Recognition of LY6K-derived peptides (e.g., RYCNLEGPPI or LLLLTVLTV) presented by MHC class I molecules (e.g., HLA-A*24:02 or HLA-A*02:01), leading to T-cell activation, cytokine release, and targeted lysis of LY6K-expressing tumor cells.