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Kita-Kyushu lung cancer antigen 1 (KK-LC-1), also known as Cancer/testis antigen 83 (CT83), is a cancer-testis antigen encoded by the CXorf61 gene [UniProt: Q5H9S0]. It is characterized by high expression in various epithelial cancers, such as non-small cell lung cancer, gastric cancer, and triple-negative breast cancer, while its expression in normal tissues is limited to the immune-privileged testis [Fukuyama et al., 2006; PubMed: 16452219]. This expression profile makes KK-LC-1 an attractive target for T-cell-based immunotherapies. The target specifically consists of peptide epitopes, such as the HLA-A*01:01-restricted RQIKIWFQK sequence, which are processed and presented on the surface of tumor cells by Major Histocompatibility Complex (MHC) molecules [Pasetto et al., 2020; PubMed: 33106341]. Therapeutic interventions, particularly T-cell receptor (TCR) engineered T-cell therapies, are designed to recognize these peptide-MHC complexes with high specificity [ClinicalTrials.gov: NCT05486884]. Upon binding, these engineered T cells trigger a cytotoxic response, leading to the selective destruction of antigen-positive tumor cells. Current clinical research is exploring the efficacy of these TCR-T therapies in patients with advanced solid tumors expressing KK-LC-1 [NIH/NCI].
T-cell receptor (TCR) mediated recognition of peptide-MHC complexes leading to T-cell activation and targeted lysis of tumor cells.
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