DEP domain containing 1-derived peptide–HLA class I complex (DEPDC1-HLA-I complex)

The DEP domain containing 1-derived peptide–HLA class I complex is a specialized molecular target consisting of a short immunogenic peptide derived from the DEPDC1 protein presented by Human Leukocyte Antigen (HLA) class I molecules. DEPDC1 is a cancer-testis-like antigen that is highly overexpressed in various malignancies, such as bladder and lung cancers, but has restricted expression in normal adult tissues, making its peptide-HLA complex an ideal target for immunotherapy (Obara et al., 2012, Cancer Science). On the surface of antigen-presenting cells (APCs), this complex serves to prime and expand specific cytotoxic T lymphocytes (CTLs), while on tumor cells, it acts as the recognition site for these CTLs to execute cell-mediated killing (Yuan et al., 2014, World Journal of Gastroenterology). Therapeutic interventions targeting this complex primarily involve peptide-based vaccines, such as the DEPDC1-9-294 peptide, which are designed to stimulate a robust anti-tumor immune response in patients with HLA-matched profiles, particularly HLA-A*24:02 (NCT00910598). Clinical studies have indicated that the presence of this complex and the subsequent induction of specific CTLs correlate with improved clinical outcomes and survival in patients with advanced bladder cancer. Because DEPDC1 plays a role in cell cycle regulation and its downregulation leads to growth inhibition, targeting the DEPDC1-HLA complex provides a dual advantage of attacking a protein essential for tumor cell proliferation while minimizing damage to healthy cells.

Other names

DEPDC1 peptide-MHC complexDEPDC1-HLA-A*24:02 complexDEPDC1-derived epitope-HLA complexDEP domain containing 1-derived peptide-MHC class I complex

Induction and activation of peptide-specific cytotoxic T lymphocytes (CTLs) that recognize the DEPDC1-HLA complex on the surface of tumor cells, leading to targeted cell lysis.