Human leukocyte antigen A*2402–Vascular endothelial growth factor receptor 1 peptide complex (HLA-A*2402–VEGFR1)

The Human leukocyte antigen A*2402–Vascular endothelial growth factor receptor 1 (VEGFR1) peptide complex is a molecular assembly consisting of the HLA-A*2402 major histocompatibility complex (MHC) class I molecule and a specific antigenic peptide derived from the VEGFR1 protein, typically the VEGFR1-1084 epitope (SYGVLLWEI) [1.2.4, 1.4.1]. This complex is a key target in cancer immunotherapy, particularly for patients who are HLA-A*2402 positive, an allele highly prevalent in East Asian populations [1.5.1]. The biological function of this complex is to present the VEGFR1-derived antigen to the immune system, specifically to CD8+ cytotoxic T lymphocytes (CTLs) [1.3.2]. When recognized by T-cell receptors, the complex triggers an immune-mediated attack against cells expressing VEGFR1, which include both tumor cells and the endothelial cells of the tumor's neo-vasculature [1.2.1, 1.2.3]. By targeting these cells, drugs such as peptide vaccines aim to inhibit tumor angiogenesis and induce direct tumor cell lysis [1.3.2]. Clinical development has focused on using this complex to treat various solid tumors, including gastric, pancreatic, and renal cell carcinomas, where it has shown potential in inducing specific immune responses with a favorable safety profile [1.2.2, 1.4.1].

Other names

HLA-A*24:02-VEGFR1 complexHLA-A24-restricted VEGFR1 peptide complexVEGFR1-1084 peptide-HLA-A*2402 complexHLA-A*2402-VEGFR1-1084

The peptide vaccine (e.g., VEGFR1-1084) binds to the HLA-A*2402 molecule to form a stable complex on the surface of antigen-presenting cells or target cells [1.4.1]. This complex is specifically recognized by the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes (CTLs), triggering an immune response that leads to the lysis of VEGFR1-expressing cells, such as tumor-associated endothelial cells, thereby inhibiting tumor angiogenesis and growth [1.2.1, 1.3.2].