Collagen type VI and other native Anthrax toxin receptor 1 (TEM8) ligands (TEM8 ligands)

Anthrax toxin receptor 1 (ANTXR1), also known as Tumor Endothelial Marker 8 (TEM8), is a cell surface protein that is highly overexpressed on the vasculature of various solid tumors while remaining minimally expressed in normal adult tissues (Nanda et al., 2004, PubMed: 15121885). Its primary physiological ligand is Collagen type VI, specifically the alpha 3 chain (COL6A3), an extracellular matrix protein that plays a critical role in maintaining tissue integrity and signaling (Hotchkiss et al., 2005, PubMed: 15601767). The interaction between TEM8 and Collagen VI promotes endothelial cell migration, proliferation, and tube formation, thereby facilitating tumor angiogenesis and progression (Werner et al., 2006, PubMed: 16707441). In addition to Collagen VI, TEM8 can interact with other native ligands in the tumor microenvironment to modulate signaling pathways like Wnt/beta-catenin. Therapeutic strategies targeting this axis include monoclonal antibodies like ontuxizumab (MORAb-004) and chimeric antigen receptor (CAR) T-cells designed to disrupt the TEM8-ligand interaction or selectively kill TEM8-expressing cells (Chaudhary et al., 2012, PubMed: 22491545). While promising for its tumor-selective expression, challenges include ensuring minimal toxicity to healthy tissues where low levels of TEM8 or its ligands may exist, such as in the skin or lungs (UniProt: Q9H6X2).

Other names

COL6Collagen VIANTXR1 ligandsTumor endothelial marker 8 ligandsCOL6A3

Inhibition of ligand binding to TEM8, disruption of tumor-associated angiogenesis, and antibody-dependent cellular cytotoxicity (ADCC).