Kita-Kyushu lung cancer antigen 1 peptide presented by Human Leukocyte Antigen B*15 or A*01:01 (KK-LC-1/HLA-B*15 or HLA-A*01:01)

Kita-Kyushu lung cancer antigen 1 (KK-LC-1), also known as Cancer/testis antigen 83 (CT83), is a germline-encoded protein that serves as a highly specific target for cancer immunotherapy due to its restricted expression in malignant tissues and immunologically privileged sites like the testis (Fukuyama et al., 2006, Cancer Res). The target specifically refers to immunogenic peptides derived from the KK-LC-1 protein that are processed and presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules, specifically the HLA-B*15 or HLA-A*01:01 alleles (Pasetto et al., 2023, JITC). These peptide-MHC (pMHC) complexes are recognized by the T-cell receptors (TCRs) of cytotoxic T lymphocytes, which then initiate a targeted immune response against the cancer cell (Leko et al., 2019, JCI Insight). Therapeutic strategies targeting this complex primarily involve TCR-engineered T-cell (TCR-T) therapies, which are currently being evaluated in clinical trials for patients with KK-LC-1-positive solid tumors such as non-small cell lung cancer, gastric cancer, and cervical cancer (National Cancer Institute, NCT05486884). Because KK-LC-1 is not expressed in essential normal tissues, these therapies aim to achieve high tumor specificity with minimal on-target off-tumor toxicity.

Other names

CT83Cancer/testis antigen 83KK-LC-1 peptide-MHC complexKita-Kyushu lung cancer antigen 1

Engineered T-cell receptors (TCRs) bind to the KK-LC-1 peptide presented by specific HLA alleles, triggering T-cell activation, cytokine release, and cytotoxic lysis of the target tumor cell.