Cancer-testis antigen 83 (KK-LC-1) peptide–HLA-A*01:01 complex (CT83/KK-LC-1–HLA-A*01:01)

The Cancer-testis antigen 83 (CT83/KK-LC-1) peptide–HLA-A*01:01 complex is a specific peptide-major histocompatibility complex (pMHC) that serves as a target for T-cell-based immunotherapies (Fukuyama et al., 2006, PMID: 16758561). CT83, also known as Kita-Kyushu lung cancer antigen 1 (KK-LC-1), is a cancer-testis antigen that is highly expressed in several malignancies, including non-small cell lung cancer, gastric cancer, and triple-negative breast cancer (Shida et al., 2012, PMID: 22552458). In contrast, its expression is restricted in healthy somatic tissues, primarily limited to the testis, which lacks HLA expression and is an immune-privileged site. The HLA-A*01:01 allele presents specific immunogenic peptides derived from the KK-LC-1 protein on the surface of tumor cells. This complex is recognized by the T-cell receptors (TCRs) of cytotoxic T lymphocytes, triggering an immune response and subsequent tumor cell lysis. Because of its high tumor-selective expression pattern, this pMHC complex is an attractive target for TCR-engineered T-cell (TCR-T) therapies. Therapeutic candidates like TK-8001 are designed to specifically bind this complex to treat patients with solid tumors (T-knife Therapeutics, 2023). Clinical development focuses on patients who are both HLA-A*01:01 positive and have KK-LC-1-expressing tumors, representing a precision oncology approach.

Other names

KK-LC-1–HLA-A*01:01 complexCT83–HLA-A*01:01 complexKita-Kyushu lung cancer antigen 1–HLA-A*01:01 complexKK-LC-1(76-84)–HLA-A*01:01

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to cytotoxic T-lymphocyte (CTL) activation and tumor cell lysis.