ArticleBiomaterials2012
Anti-CD20 multivalent HPMA copolymer-Fab' conjugates for the direct induction of apoptosis.
Article in Biomaterials, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 59 citations in OpenAlex.
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- Human Serum Albumin-Based Drug-Free Macromolecular Therapeutics: Apoptosis Induction by Coiled-Coil-Mediated Cross-Linking of CD20 Antigens on Lymphoma B Cell Surface.Macromolecular bioscience · 2018Article
- Drug-free macromolecular therapeutics: Impact of structure on induction of apoptosis in Raji B cells.Journal of controlled release : official journal of the Controlled Release Society · 2017Article
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- Design of smart HPMA copolymer-based nanomedicines.Journal of controlled release : official journal of the Controlled Release Society · 2016Review
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- Tracking and quantifying polymer therapeutic distribution on a cellular level using 3D dSTORM.Journal of controlled release : official journal of the Controlled Release Society · 2016Article
- Polymeric drugs: Advances in the development of pharmacologically active polymers.Journal of controlled release : official journal of the Controlled Release Society · 2015Review
- POLYMERIC BIOMATERIALS AND NANOMEDICINES.Journal of drug delivery science and technology · 2015Article
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Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
A hybrid biomimetic system comprising high-molecular-weight, linear copolymer of N-(2-hydroxypropyl)methacrylamide (HPMA) grafted with multiple Fab' fragments of anti-CD20 monoclonal antibody (mAb) was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization followed by attachment of Fab' fragments via thioether bonds. Exposure of human non-Hodgkin's lymphoma (NHL) Raji B cells to the multivalent conjugates resulted in crosslinking of CD20 receptors and commencement of apoptosis. Five conjugates with varying molecular weight and valence (amount of Fab' per polymer chain) were synthesized. One of the copolymers contained enzyme degradable peptide sequences (GFLG) in the backbone. The multivalency led to higher avidity and apoptosis induction compared to unconjugated whole mAb. Time-dependent studies showed that the cytotoxicity of conjugates exhibited a slower onset at shorter exposure times than mAb hyper-crosslinked with a secondary Ab; however, at longer time intervals the HPMA copolymer conjugates achieved significantly higher biological efficacies. In addition, study of the relationship between the structure of conjugates and Raji B cell apoptosis revealed that both valency and polymer molecular weight influenced biological activities, while insertion of peptide sequences into the backbone was not a factor in vitro.
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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.