VHH nanobody-masked CDH17xCD3 T cell engager

VHH nanobody-masked CDH17xCD3 T cell engager is a conditionally active bispecific T cell engager (TCE) developed by WuXi Biologics for the treatment of solid tumors, specifically colorectal cancer. The molecule is designed to target Cadherin-17 (CDH17), a protein highly expressed in colorectal cancers but also present in normal intestinal and pancreatic tissues. To enhance safety and reduce off-tumor toxicity, the drug utilizes a proprietary masking platform where the CD3-binding arm is shielded by an anti-idiotypic VHH nanobody. This mask is connected via a linker that is selectively cleaved by proteases, such as matrix metalloproteinases (MMPs), which are prevalent in the tumor microenvironment. Upon cleavage, the TCE becomes active, facilitating the recruitment and activation of T cells against CDH17-expressing tumor cells. Preclinical data have shown that this masked TCE maintains systemic stability while providing potent anti-tumor activity and an improved safety profile compared to non-masked versions. The CD3-binding component is derived from a clinical-stage CD3 binder (NCT05579132).

Other names

conditionally active CDH17 TCEVHH-masked CDH17xCD3 TCEVHH-masked CD3 TCE