Vascular endothelial growth factor receptor 2-derived peptide presented by human leukocyte antigen class I (VEGFR2-peptide/HLA-I)

The Vascular endothelial growth factor receptor 2 (VEGFR2)-derived peptide presented by human leukocyte antigen (HLA) class I is a specialized antigenic complex used in cancer immunotherapy to target tumor angiogenesis (Mizukoshi et al., 2011, Cancer Science). VEGFR2, also known as KDR, is a primary driver of new blood vessel formation and is highly upregulated on the endothelial cells of the tumor microenvironment (UniProt P35968). When VEGFR2 proteins are degraded within these cells, specific peptide fragments, such as the VEGFR2-169 (VLLAVALWL) epitope, are loaded onto HLA class I molecules and displayed on the cell surface for recognition by CD8+ T cells (Schmitz-Winnenthal et al., 2015, OncoImmunology). Therapeutic strategies, including DNA vaccines like VXM01 and adoptive T-cell therapies like TBI-1501, are designed to prime or engineer the immune system to recognize these specific pMHC complexes (NCT01486329). By directing a cytotoxic immune response against VEGFR2-presenting endothelial cells, these treatments aim to collapse the tumor's vascular network, thereby inhibiting tumor growth and metastasis. However, because VEGFR2 is also present on some healthy endothelial cells, potential safety concerns include on-target off-tumor toxicities such as hypertension or impaired wound healing. This target represents a strategy to starve tumors of nutrients and oxygen by disrupting their supporting infrastructure.

Other names

KDR-derived peptide/HLA complexVEGFR2-pMHCHLA-restricted VEGFR2 antigenVEGFR2-169 peptideHLA-A*02:01-restricted VEGFR2 peptide

Induction of a cytotoxic T-lymphocyte (CTL) response against tumor-associated endothelial cells presenting VEGFR2-derived peptides, leading to the disruption of tumor blood supply (Schmitz-Winnenthal et al., 2015).