Biological Activity of Anti-CD20 Multivalent HPMA Copolymer-Fab’ Conjugates

• Published in: Biomacromolecules Vol. 13; no. 3; pp. 727 - 735
• Main Authors: Johnson, Russell N, Kopečková, Pavla, Kopeček, Jindřich
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 12.03.2012
• Subjects: Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - pharmacology; Antigens, CD20 - metabolism; Applied sciences; Biological and medical sciences; Drug Delivery Systems; Drug Design; Exact sciences and technology; General pharmacology; Humans; Immunoglobulin Fab Fragments - chemistry; Immunoglobulin Fab Fragments - pharmacology; Lymphoma, B-Cell - drug therapy; Lymphoma, B-Cell - immunology; Medical sciences; Methacrylates - chemistry; Methacrylates - pharmacology; Organic polymers; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemistry of polymers; Polymers - chemistry; Polymers - pharmacology; Polymers with particular properties; Preparation, kinetics, thermodynamics, mechanism and catalysts; Tumor Cells, Cultured; Monoclonal antibody; Fab-Fragment; Experimental study; Biological activity; Lateral group; Chemical coupling; Dose activity relation; Methacrylamide derivative copolymer; Alcohol copolymer; Chemical modification; Cell line; Preparation; Radical copolymerization; Amine copolymer; Apoptosis
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm201656k

High-molecular-weight, branched N-(2-hydroxypropyl)­methacrylamide (HPMA) copolymers were synthesized and conjugated with Fab’ fragments of the anti-CD20 antibody, 1F5. This produced multivalent conjugates with varying valency (amount of Fab’ per macromolecule) targeted to the B-cell antigen CD20. The apoptotic activity of the conjugates was screened against several B-cell lymphomas with varied expression levels of CD20 (Raji, Daudi, Ramos, Namalwa, and DG-75). The multivalent conjugates had the strongest activity against cells that had the highest expression of CD20 and failed to demonstrate any measurable activity against lymphomas that did not express the antigen. Furthermore, there was an apparent dose-dependent response to treatment with multivalent conjugates. At optimal valence and concentration, the apoptotic activity of HPMA copolymer-Fab’ conjugates superseded that of free anti-CD20 Ab that was hyper-cross-linked with a polyclonal, secondary Ab.