TGW101-ADC + TRG001

TGW101-ADC + TRG001 is a first-in-class, two-component combination therapy comprising a click-cleavable antibody-drug conjugate (TGW101-ADC) and a trigger molecule (TRG001). TGW101-ADC is a diabody antibody targeting the non-internalizing pan-carcinoma marker TAG-72, conjugated to the cytotoxic payload monomethyl auristatin E (MMAE) via a highly reactive trans-cyclooctene (TCO) linker. TRG001 is a tetrazine-based small molecule trigger administered intravenously 48 hours after TGW101-ADC; binding of TGW101-ADC to tumor TAG-72 is followed by systemic administration of TRG001, which triggers rapid and highly selective cleavage of the linker at the tumor site, leading to extracellular release of MMAE in the tumor microenvironment and cytotoxicity to surrounding cancer cells. This technology allows for payload release at the tumor without internalization, transforming non-internalizing antigens into actionable ADC targets and maximizing antitumor bystander effects. Preclinical studies show potent, dose-dependent tumor regression only in the presence of both TGW101-ADC and TRG001, with favorable tolerability and minimal off-tumor toxicity. The therapy is being developed for advanced solid tumors, particularly those expressing TAG-72, including ovarian, colorectal, gastric, and pancreatic cancers[1][3][5].

Other names

TGW101-ADC + TRG001TAG-72-targeting Click-to-Release ADCTAG72-targeting Click-to-Release ADCTAG 72-targeting Click-to-Release ADC