We describe the preclinical development of m825-MMAE, a TEM8 ADC with potent tumor-regressing activity against multiple cancer types and an unexpected tumor-killing mechanism that depends on tumor-associated stroma. TEM8 is broadly expressed in …

2018年7月2日 · Here, we describe a potent MMAE-linked antibody-drug conjugate (ADC) targeting tumor endothelial marker 8 (TEM8, also known as ANTXR1), a highly conserved transmembrane receptor broadly overexpressed on cancer …

Tumor endothelial marker 8 (TEM8) is a highly conserved transmembrane receptor broadly overexpressed on cancer-associated fibroblasts, endothelium, and pericytes. An ADC targeting TEM8 localized to tumor stroma and released MMAE in stromal cells to kill nearby proliferating tumor cells in a target-independent manner (Szot et al., 2018).

2018年6月4日 · TEM8-ADC kills cancer cells via a bystander mechanism dependent on TEM8-expressing tumor stroma. The efficacy of the TEM8-ADC (i) as an antitumor agent is driven by DAaRTS. TEM8 expression in the tumor stroma, including fibroblasts, pericytes, and endothelial cells, localizes MMAE-linked TEM8-ADC to growing tumors (ii).

2023年10月25日 · Approaches that target the tumor stroma rather than cancer cells, e.g. glypican-1 on CAFs or tumor endothelial marker 8 (TEM8) on CAFs, endothelium and pericytes present as a promising approach moving forward. These strategies may help to bypass the poor internalization and trafficking of tumor associated antigens and deliver free drug to the ...

Researchers at the National Cancer Institute (NCI) have developed fully human monoclonal antibodies and antibody-drug conjugates (ADCs) that target TEM8. The antibodies and ADCs have been tested both in vitro and in vivo and have shown promising data.

2012年2月14日 · TEM8 is an appealing target for selective inhibition of tumor angiogenesis because it is functionally required for optimal tumor angiogenesis and growth but dispensable for normal development and physiological angiogenesis.

2018年7月2日 · TEM8-ADC kills cancer cells via a bystander mechanism dependent on TEM8-expressing tumor stroma. The efficacy of the TEM8-ADC (i) as an antitumor agent is driven by DAaRTS. TEM8 expression in the tumor stroma, including fibroblasts, pericytes, and endothelial cells, localizes MMAE-linked TEM8-ADC to growing tumors (ii).

The TEM8 targeting m825 was developed into an ADC by conjugating it with MMAE via a cleavable linker. In vivo efficacy was tested in immunodeficient nude mice in a range of tumour models including colon, breast, lung, ovarian and pancreatic tumours. m825-MMAE showed superior TGI compared to chemotherapy, with the combination of ADC and ...

We have generated promising preclinical data in TEM8/ANTXR1-directed ADC tool constructs in multiple cancers, including ovarian, breast, lung, colon, and pancreatic cancer models. In these studies, our TEM8/ANTXR1-directed ADC constructs prolonged survival, blocked metastasis, and augmented the efficacy of conventional chemotherapy agents ...