TTK protein kinase – Human leukocyte antigen A*24:02 complex (TTK-HLA-A*24:02)

The TTK – HLA-A*24:02 complex is a specific peptide-major histocompatibility complex (pMHC) target used in cancer immunotherapy. TTK, also known as Monopolar Spindle 1 (MPS1), is a dual-specificity protein kinase that plays a critical role in the spindle assembly checkpoint during mitosis, ensuring proper chromosome segregation (UniProt P33981). While TTK expression is low in most normal adult tissues, it is significantly upregulated in various malignancies, including esophageal, gastric, and breast cancers, making it an attractive tumor-associated antigen (PMID: 18483244). The HLA-A*24:02 allele is one of the most prevalent MHC Class I alleles in East Asian populations, particularly in Japan (Allele Frequency Net Database). Therapeutic strategies targeting this complex include peptide vaccines, such as TTK-567, and engineered T-cell receptor (TCR) therapies designed to induce or provide cytotoxic T lymphocytes that specifically recognize and eliminate tumor cells presenting this epitope (PMID: 24333713). These interventions leverage the immune system's ability to identify intracellular oncogenic proteins through surface-presented fragments. Clinical trials have demonstrated that vaccination with TTK-derived peptides can safely induce specific immune responses in patients with advanced cancers (PMID: 28455777). The specificity of this complex allows for a targeted approach that minimizes damage to healthy cells lacking the HLA-A*24:02/TTK combination.

Other names

TTK-567 peptide – HLA-A*24:02 complexMPS1 – HLA-A*24:02 complexTTK-HLA-A24 complexTTK-567-A24

Activation of antigen-specific cytotoxic T lymphocytes (CTLs) or direct targeting by engineered T-cell receptors (TCRs) that recognize the TTK-derived peptide presented by the HLA-A*24:02 molecule on the surface of cancer cells, resulting in targeted apoptosis of the malignant cells (PMID: 24333713).