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Kita-Kyushu lung cancer antigen 1 (KK-LC-1), also known as Cancer/Testis Antigen 83 (CT83), is a member of the cancer-testis antigen family. It is characterized by high expression in various malignancies, including lung, gastric, and breast cancers, while its expression in normal tissues is restricted primarily to the testis, which lacks HLA expression. This expression profile makes the KK-LC-1 peptide, when presented by the Human Leukocyte Antigen (HLA)-A*01 allele, an ideal target for adoptive cell therapies. The complex is specifically recognized by engineered T-cell receptors (TCR-T), which trigger a potent cytotoxic immune response against tumor cells. Clinical development focuses on using these TCR-T cells to treat patients whose tumors express KK-LC-1 and who carry the HLA-A*01:01 genotype. Because the testis is an immune-privileged site, the risk of systemic autoimmune toxicity is considered lower compared to other tumor-associated antigens.
Recognition of the specific KK-LC-1 peptide presented by HLA-A*01 molecules on the surface of tumor cells by engineered T-cell receptors (TCRs), leading to T-cell activation, cytokine release, and targeted lysis of the cancer cell.
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