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daratumumab + N-(2-hydroxypropyl)methacrylamide copolymer + monomethyl auristatin E
- Development stage
- Preclinical
- Lead developer
- Institute of Macromolecular Chemistry, Czech Academy of Sciences
- Modality
- Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics, Biodegradable Polymers → Polymer-based Nanoparticles → Nanoparticles → Drug Delivery Systems
- Administration
- Intravenous
01
Overview
**Daratumumab + N-(2-hydroxypropyl)methacrylamide copolymer + monomethyl auristatin E** is an experimental CD38-targeted antibody-polymer-drug conjugate nanomedicine developed for relapsed or refractory B-cell non-Hodgkin lymphoma. The construct covalently combines the anti-CD38 monoclonal antibody daratumumab with an HPMA-based copolymer scaffold carrying monomethyl auristatin E through a lysosomally cleavable valine-citrulline-para-aminobenzyl carbamate linker. Daratumumab directs the conjugate to CD38-positive lymphoma cells and promotes cellular internalization; intracellular linker cleavage releases MMAE, which inhibits tubulin polymerization and causes mitotic arrest and apoptosis. The HPMA polymer architecture is intended to enable a higher drug-to-antibody ratio than a conventional antibody-drug conjugate while maintaining antibody conjugation characteristics.
02
Targets
CD38 (Cluster of Differentiation 38)
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