title: Biological activity of anti-CD20 multivalent HPMA copolymer-Fab' conjugates.
abstract: 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 At optimal valence and concentration, the apoptotic activity of HPMA copolymer-Fab' conjugates superseded that of free anti-CD20 Ab that was hyper-cross-linked with a polyclonal, secondary Ab.
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, Utah 84112, United States.
authors.forename: Russell N
authors.initials: RN
authors.lastname: Johnson
authors.forename: Pavla
authors.initials: P
authors.lastname: Kopečková
authors.forename: Jindřich
authors.initials: J
authors.lastname: Kopeček
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology*; D018951:Antigens, CD20 / Q000378:metabolism*; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry* / Q000494:pharmacology; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000276:immunology; D008689:Methacrylates / Q000737:chemistry* / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D007140:Immunoglobulin Fab Fragments; D008689:Methacrylates; D011108:Polymers; C032802:hydroxypropyl methacrylate