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Rational payload selection enables high antitumoral efficacy of an anti-EGFR antibody-drug conjugate against ovarian tumors - PubMed

6 hours ago
  • #Ovarian cancer
  • #Targeted therapy
  • #Antibody-drug conjugate
  • EGFR is frequently expressed in ovarian cancer but remains an underexplored therapeutic target.
  • Cetuximab-based ADCs with payloads (DM1, DXd, MMAF) were evaluated for efficacy against ovarian cancer.
  • MMAF-conjugated ADCs, especially cetuximab-vc-MMAF, showed superior antiproliferative effects in high-EGFR-expressing cells.
  • Cetuximab-vc-MMAF demonstrated rapid internalization, lysosomal trafficking, and induced G2/M arrest, DNA damage, and apoptosis.
  • In vivo studies confirmed cetuximab-vc-MMAF's tumor growth inhibition, prolonged survival, and selective intratumoral accumulation without systemic toxicity.
  • The findings support further preclinical and clinical development of EGFR-targeting ADCs for ovarian cancer.