Antibody-drug conjugate combination therapy targeting LGR5 and MET with different payloads enhances efficacy in preclinical colorectal cancer models

Combining LGR5- and MET-targeting ADCs with different payloads significantly delays tumor relapse and prolongs survival in preclinical colorectal cancer models.

• Why it matters: Overcoming tumor recurrence due to LGR5 downregulation remains a challenge in CRC therapy, highlighting the need for strategies that target both cancer stem-like cells and receptor pathways to improve outcomes.
• What they did: Researchers engineered a MET-targeting ADC (ABT-700-SG3199) with superior potency and combined it with an LGR5-targeting ADC carrying a topoisomerase 1 inhibitor (8E11-CPT2), testing their effects in CRC models and patient-derived xenografts.
• The result: The dual-targeting approach increased LGR5 expression, enhanced tumor cell killing, and markedly delayed relapse, suggesting that simultaneous targeting of LGR5 and MET may overcome resistance and improve therapeutic efficacy.