ArticleMolecular cancer therapeutics2023
A Bispecific METxMET Antibody-Drug Conjugate with Cleavable Linker Is Processed in Recycling and Late Endosomes.
Article in Molecular cancer therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 17 citations in OpenAlex.
- Cathepsin Family Proteases in Prodrug Design: Recent Advances.ChemMedChem · 2026Review
- Article
- Drug resistance to antibody-drug conjugates: mechanisms, challenges, and perspectives.Cancer biology & medicine · 2026Review
- Antibody-drug conjugates in cancer therapy: current landscape, challenges, and future directions.Molecular cancer · 2025Review
- Recent Advances in Bioanalytical Methods for Quantification and Pharmacokinetic Analyses of Antibody-Drug Conjugates.The AAPS journal · 2025Review
- Advancements in antibody-drug conjugates as cancer therapeutics.Journal of the National Cancer Center · 2025Review
- Fluorogenic Platform for Real-Time Imaging of Subcellular Payload Release in Antibody-Drug Conjugates.Journal of the American Chemical Society · 2025Article
- The mechanisms of HER2 targeted ADCs are dependent on Rab GTPases.Therapeutic advances in medical oncology · 2025Article
- Progress of antibody-drug conjugates (ADCs) targeting c-Met in cancer therapy; insights from clinical and preclinical studies.Drug delivery and translational research · 2024Review
- Unlocking the potential of bispecific ADCs for targeted cancer therapy.Frontiers of medicine · 2024Review
- Review
- Bispecific antibody drug conjugates: Making 1+1>2.Acta pharmaceutica Sinica. B · 2024Review
- The present and future of bispecific antibodies for cancer therapy.Nature reviews. Drug discovery · 2024Review
- Exploring the next generation of antibody-drug conjugates.Nature reviews. Clinical oncology · 2024Review
- Antibody-drug conjugates combinations in cancer treatment.Exploration of targeted anti-tumor therapy · 2024Review
- Article
- Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most antibody-drug conjugates (ADC) approved for the treatment of cancer contain protease-cleavable linkers. ADCs that traffic to lysosomes traverse highly acidic late endosomes, while ADCs that recycle to the plasma membrane traffic through mildly acidic sorting and recycling endosomes. Although endosomes have been proposed to process cleavable ADCs, the precise identity of the relevant compartments and their relative contributions to ADC processing remain undefined. Here we show that a METxMET biparatopic antibody internalizes into sorting endosomes, rapidly traffics to recycling endosomes, and slowly reaches late endosomes. In agreement with the current model of ADC trafficking, late endosomes are the primary processing site of MET, EGFR, and prolactin receptor ADCs. Interestingly, recycling endosomes contribute up to 35% processing of the MET and EGFR ADCs in different cancer cells, mediated by cathepsin-L, which localizes to this compartment. Taken together, our findings provide insight into the relationship between transendosomal trafficking and ADC processing and suggest that receptors that traffic through recycling endosomes might be suitable targets for cleavable ADCs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.