The article “Chemically triggered drug release from an antibody-drug conjugate leads to potent antitumour activity in mice” published in Nature Communications by Raffaella Rossin et al. describes the successful use of ‘click-to-release’ chemistry in ADC (antibody drug conjugate) pretargeting therapy, as demonstrated pre-clinically in mice studies.
The research has been led by Tagworks Pharmaceuticals, and has comprised collaborative efforts from SyMO-Chem (the Netherlands), Avipep (Australia), Levena Biopharma (USA), Syncom (the Netherlands) and the Radboud University (the Netherlands). The approach of the research involves the administration of a non-internalizing ADC that targets and accumulates in the tumour, and that can thereafter react in a controlled fashion with an activator molecule that is administered once the ADC has cleared from the rest of the body. The activator molecule reacts fast and selectively with the ADC in a ‘click-to-release’ reaction, cleaving off the drug and discharging it in the local tumour environment only.
Results for the developed first-in-class ADC in the applied tumour models compare favorably to those for an analogous ADC comprising the protease-cleavable linker used in the FDA approved ADC ‘Adcetris’, and hold promise for a broader applicability of ADCs across patient populations.