CDH17-directed antibody drug conjugate

CDH17-directed antibody-drug conjugates (ADCs) represent a therapeutic class targeting Cadherin 17 (CDH17), a calcium-dependent adhesion protein highly expressed in gastrointestinal malignancies, particularly colorectal cancer (CRC). These agents consist of a humanized monoclonal antibody specific to the extracellular domain of CDH17, conjugated to potent cytotoxic payloads via cleavable linkers. Preclinical research, notably from the University of California Los Angeles (UCLA), has evaluated different payload classes, including the anti-mitotic agent monomethyl auristatin E (MMAE) and the topoisomerase 1 inhibitor exatecan. Findings suggest that exatecan-based ADCs may offer superior efficacy in tumors with high P-glycoprotein (P-gp) expression, which often mediates resistance to MMAE-based payloads. However, the clinical development of CDH17-directed ADCs faces challenges such as target-mediated clearance and potential on-target, off-tumor toxicity due to CDH17 expression in normal intestinal and ileal epithelium, which can act as a pharmacokinetic sink.

Other names

CDH17 ADCCDH-17 ADCCDH 17 ADCCadherin 17-directed antibody drug conjugateCadherin17-directed antibody drug conjugateCadherin-17-directed antibody drug conjugate