Major Histocompatibility Complex class I presenting Vascular Endothelial Growth Factor Receptor 2 peptide 169 (MHC-I/VEGFR2-169)

The MHC class I presenting VEGFR2-169 peptide is a molecular complex consisting of a specific epitope derived from Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) bound to a Major Histocompatibility Complex (MHC) class I molecule. This complex, most commonly involving the HLA-A*02:01 allele, presents the amino acid sequence RFVPDGNRI (residues 169-177) on the surface of cells (Niethammer et al., 2002, PMID: 12414657). VEGFR2 is highly expressed on the vascular endothelial cells of tumors to support neoangiogenesis, making this pMHC complex a valuable tumor-associated antigen. The primary biological role of this target in a therapeutic context is to serve as a recognition site for CD8+ cytotoxic T lymphocytes. Drugs like the oral DNA vaccine VXM01 are designed to induce a T-cell mediated immune response against cells displaying this specific peptide (Schmitz-Winnenthal et al., 2015, PMID: 24583793). By targeting the tumor vasculature rather than the tumor cells themselves, this approach aims to overcome the genetic instability and heterogeneity often found in malignant cells. Clinical trials have investigated this target in various solid tumors, including pancreatic cancer and glioblastoma, to evaluate its ability to inhibit tumor growth through anti-angiogenic effects (Wick et al., 2015, PMID: 26101234). Monitoring the efficacy of such therapies often involves measuring the frequency of VEGFR2-specific T cells in the peripheral blood.

Other names

HLA-A*02:01/VEGFR2-169 complexVEGFR2-169 peptide-MHCKDR-169/HLA-A*02:01Vascular endothelial growth factor receptor 2 fragment 169-177VEGFR2(169-177) epitope

Induction of a T-cell mediated immune response where CD8+ cytotoxic T lymphocytes recognize the VEGFR2-169 peptide presented by MHC-I, leading to the selective lysis of VEGFR2-expressing tumor endothelial cells and subsequent inhibition of tumor angiogenesis (Schmitz-Winnenthal et al., 2015, PMID: 24583793).