Modular in vivo antibody-ADC click to reverse drug resistance in tumours.

Modular in vivo antibody-ADC click strategy enhances tumor targeting and overcomes resistance in heterogeneous cancers, showing improved activity in preclinical models.

• Why it matters: Current ADC therapies are limited by reliance on single antigens, leading to reduced effectiveness and resistance in tumors with variable or low antigen expression, necessitating more adaptable targeting methods.
• What they did: The researchers developed an in vivo bioorthogonal ligation platform that conjugates antibodies and ADCs with trans-cyclooctene and tetrazine groups, enabling sequential systemic administration and in situ click conjugation in tumors.
• The result: This approach improved antitumor efficacy over standard treatments in models with HER2 and EGFR co-expression, including low or heterogeneous antigen tumors, and offers a flexible platform adaptable to various receptor targets.