Endoglin Targeting: Lessons Learned and Questions That Remain

Abstract

Approximately 30 years ago, endoglin was identified as a transforming growth factor (TGF)-β coreceptor with a crucial role in developmental biology and tumor angiogenesis. Its selectively high expression on tumor vessels and its correlation with poor survival in cancer patients led to the exploration of endoglin as a therapeutic target for cancer. The endoglin neutralizing antibody TRC105 (Carotuximab®, Tracon Pharmaceuticals (San Diego, CA, USA) was subsequently tested in a wide variety of preclinical cancer models before being tested in phase I-III clinical studies in cancer patients as both a monotherapy and in combination with other chemotherapeutic and anti-angiogenic therapies. The combined data of these studies have revealed new insights into the role of endoglin in angiogenesis and its expression and functional role on other cells in the tumor microenvironment. In this review, we will summarize the preclinical work, clinical trials and biomarker studies of TRC105 and explore what these studies have enabled us to learn and what questions remain unanswered.

Potential Molecular Biomarkers of Vestibular Schwannoma Growth: Progress and Prospects

“…CD105, better known as endoglin, is a homodimeric transmembrane glycoprotein that highly expressed on activated angiogenic endothelial cells ( 141 ). Used as a marker of MVD, CD105 has proven itself as a potent prognostic indicator and a potential target for antiangiogenic therapy and chimeric antigen receptor-based T-cell (CAR-T) immunotherapy in several tumors ( 142 – 144 ). Calculated by immunohistochemically assessed CD105 expression, Gino et al.…”

“…CD105, better known as endoglin, is a homodimeric transmembrane glycoprotein that highly expressed on activated angiogenic endothelial cells (141). Used as a marker of MVD, CD105 has proven itself as a potent prognostic indicator and a potential target for antiangiogenic therapy and chimeric antigen receptor-based T-cell (CAR-T) immunotherapy in several tumors (142)(143)(144). Calculated by immunohistochemically assessed CD105 expression, Gino et al correlated the vessel cross-sectional area (VA) and vessel density (VD) with tumor dimensions and tumor growth rate in both NF2-associated VS and sporadic VS, and found a positive correlation between VD and tumor growth rate in NF2-VS, and VA and VD with tumor size in sporadic VS (37).…”

The Versatile Roles of Cancer-Associated Fibroblasts in Colorectal Cancer and Therapeutic Implications

“…Further, the selectively high expression of endoglin in CAFs and its correlation with metastasis and poor survival in CRC patients will lead to the exploration of testing it as a therapeutic target. The coincidence is that the endoglin neutralizing antibodies such as TRC105 are being tested in clinical studies in cancer patients as a monotherapy or incorporated into combinatory therapies (Liu Y. et al, 2020). These studies will enable us to learn the prospect of treating malignant CRC through targeting endoglin-expressing CAFs.…”

Endoglin/CD105-Based Imaging of Cancer and Cardiovascular Diseases: A Systematic Review

“…Based on the endoglin-expressing cells in the tumor microenvironment, i.e., angiogenic endothelial cells, subtypes of fibroblasts, and some malignant epithelial cells, specific endoglin targeting agents have been developed for cancer therapy. The most promising is most likely carotuximab (TRC105) (reviewed in [ 38 ]). TRC105 is an endoglin-binding chimeric monoclonal antibody (human/mouse), designed for minimal immunogenicity in patients.…”

“…The remaining four articles used PET to image cardiovascular disease models. (TRC105) (reviewed in [38]). TRC105 is an endoglin-binding chimeric monoclonal antibody (human/mouse), designed for minimal immunogenicity in patients.…”