Tumor blood vessel antigen-derived HLA-A2–presented peptides (TVA-HLA-A2 peptides)

Tumor blood vessel antigen-derived HLA-A2–presented peptides are a specialized class of therapeutic targets in oncology, consisting of short amino acid sequences derived from proteins overexpressed in tumor-associated endothelial cells and presented by the HLA-A*02:01 major histocompatibility complex [Schmitz et al., 2014]. These targets, such as those derived from Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) or Tumor Endothelial Marker 8 (TEM8), allow the immune system to specifically identify and destroy the neo-vasculature supporting a tumor [Niethammer et al., 2012]. Because the tumor blood supply is critical for oxygenation, nutrient delivery, and metabolic waste removal, targeting these antigens can induce widespread tumor necrosis [Zhu et al., 2017]. This approach is particularly attractive because endothelial cells are more genetically stable than tumor cells, reducing the risk of immune escape through antigen loss [Fiedler et al., 2003]. Furthermore, the target is directly accessible to circulating T cells and therapeutic agents within the bloodstream [Byrne et al., 2015]. Current clinical development focuses on vaccines like VXM01 and adoptive T-cell therapies using engineered T-cell receptors (TCRs) to recognize these specific peptide-MHC complexes [ClinicalTrials.gov, NCT01486329].

Other names

Tumor endothelial marker (TEM) peptidesAngiogenesis-associated HLA-A2-restricted antigensVEGFR2-derived HLA-A2 peptidesTumor vasculature-associated HLA-A2-presented peptides

Induction of T-cell mediated lysis of tumor-associated endothelial cells by recognizing specific peptide-HLA-A2 complexes, leading to disruption of tumor blood supply and subsequent tumor necrosis [Niethammer et al., 2012].