TORL-3-600: A Clinical-Stage CDH17-Targeted Antibody-Drug Conjugate for Advanced Cancers

1. Introduction to TORL-3-600

TORL-3-600 (also designated TORL3600) is a novel, first-in-human antibody-drug conjugate (ADC) currently undergoing clinical investigation for the treatment of advanced malignancies.[1] Developed by TORL BioTherapeutics, LLC, this agent represents a targeted therapeutic strategy directed against Cadherin 17 (CDH17), a cell surface protein with restricted expression in normal tissues but notable overexpression in certain gastrointestinal cancers.[2]

TORL-3-600 belongs to the ADC therapeutic class, which combines the target specificity of a monoclonal antibody (mAb) with the potent cell-killing activity of a cytotoxic payload.[2] This approach aims to deliver chemotherapy selectively to cancer cells expressing the target antigen, potentially enhancing efficacy while minimizing systemic toxicity compared to traditional chemotherapy.[11] The design of TORL-3-600 involves a fully humanized mAb directed against CDH17, conjugated via a cleavable linker to the microtubule-disrupting agent monomethyl auristatin E (MMAE).[6] The intended mechanism involves binding to CDH17 on tumor cells, internalization, lysosomal trafficking, linker cleavage, and intracellular release of MMAE, leading to cell cycle arrest and apoptosis.[2]

TORL BioTherapeutics operates through an exclusive strategic partnership with the Slamon Research Laboratory at the University of California, Los Angeles (UCLA), a center recognized for its contributions to identifying key cancer targets like HER2 and CDK4/6.[7] TORL-3-600 emerged from this collaboration, which aims for rapid translation of validated preclinical findings into clinical development.[7]