Summary
CDH17 is a well-validated, highly specific target for colorectal cancer, with high and uniform tumor-antigen coverage across CRC patients and minimal expression in critical normal tissues, enabling a broad therapeutic window. We developed a CD3xCDH17 bsAb with potent in vitro cytotoxicity and superior in vivo anti-tumor activity compared with ARB202. Building on the CD3xCDH17 platform, we integrated a CD28 costimulatory domain to generate a trispecific TCE molecule with the following features:
TAA-dependent in vitro cytotoxicity
No CDH17-independent T cell fratricide observed
Superior in vitro cytotoxicity and in vivo anti-tumor activity
Building on the trispecific TCE platform, we generated a next-generation molecule with dual CDH17 targeting through incorporation of an additional CDH17 arm.
Superior in vitro cytotoxicity and in vivo anti-tumor activity
Sustained T cell cytotoxic function after multiple rounds of antigen stimulation
Favorable safety profile in mouse models
Good developability
