Table 2 Tumor endothelial cell antigens investigated as targets of ValloVax™

Vascular endothelial growth factor receptor-1 (VEGFR-1); fms-like tyrosine kinase (flt)-1

Receptor that binds VEGF with high affinity

Dominant receptor in the tumor microenvironment that is required for endothelial cell survival

[70, 71]

Vascular endothelial growth factor receptor-2 (VEGFR2); Flk-1, KDR

Also known as FLK-1 and KDR

Binds to VEGF and is considered the most important receptor with regard to tumor angiogenesis

Expressed on proliferating endothelium

Low expression on healthy vascular endothelium

[62, 72]

Endoglin/CD105

Selectively expressed by endothelial cells undergoing vasculogenesis, angiogenesis, and inflammation

Promotes endothelial cell proliferation, migration, and tube formation during early development and in tumors

[73–78]

Fibroblast growth factor receptor (FGFR)

Bind to fibroblast growth factor family members, having diverse roles in organogenesis, proliferation, pro-survival cell signaling and cellular migration

FGF/FGFR system contributes to both adult angiogenesis and tumor angiogenesis

FGFR signaling is implicated in escape of tumor vasculature from VEGF inhibitor treatment

[61, 79–82]

Integrin αvβ3; CD51/CD61

An extracellular matrix adhesion receptor that coordinates endothelial cell responses during angiogenesis

Expressed in neo-angiogenic vessels; therefore, it is upregulated in the vasculature of solid tumors, while expression is low in quiescent vasculature

[83–87]

Tumor endothelial marker 1 (TEM1); endosialin or CD248

One of the most abundantly expressed proteins on tumor vasculature and tumor stroma of human tumors

Expression is variable among tumor types; however, this protein can reportedly be expressed on endothelial cells, pericytes, and/or fibroblasts of human and animal tumors

[67, 88–93]