ArticleCommunications biology2024
Proteolysis targeting chimera (PROTAC)-driven antibody internalization of oncogenic cell surface receptors.
Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed.
- Emerging organoids and organoids-on-chip platforms for translational development of antibody‒drug conjugates and next-generation bioconjugates.Acta pharmaceutica Sinica. B · 2026Review
- Engineering Antibodies into Targeted Chimeras: From Recognition Modules to Programmable Degraders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Advances and Future Directions in Antibody-Drug Conjugates: From Paradigm Shifts to Data-Driven Design.Cancers · 2026Review
- Antibody-drug conjugates for infectious and neglected tropical diseases: chemical design principles, target biology, and translational challenges.Frontiers in chemistry · 2026Review
- Exploring Experimental and In Silico Approaches for Antibody-Drug Conjugates in Oncology Therapies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Optimization of CAR-T therapy based on metabolic remodeling of the tumor immune microenvironment in diffuse large B-cell lymphoma.American journal of cancer research · 2025Review
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibody-drug conjugates (ADCs) are increasingly used in clinic for multiple indications and may improve upon the activity of parental antibodies by delivering cytotoxic payloads into target cells. This activity is predicated upon internalization to release the cytotoxic payloads intracellularly. Since binding of ADCs to their cell surface targets does not guarantee their internalization, we hypothesize that proteolysis targeting chimeras (PROTACs) could improve the activity of ADCs through forced internalization. We show that PROTACs improve internalization of antibodies or their derivative antibody drug conjugates when both agents target the same oncogenic cell surface proteins (EGFR, HER2 or MET) by 1.4-1.9 fold in most models. PROTACs also significantly enhance cytotoxicity with HER2-targeting ADCs. These effects depend on dynamin and proteolysis. This application of PROTACs may impact the use of ADCs and provides a rationale to combine these agents in clinical trials.
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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.