Warning: Undefined array key "mm" in /www/wwwroot/www.ai-bt.com/si.php on line 10 Deprecated: trim(): Passing null to parameter #1 ($string) of type string is deprecated in /www/wwwroot/www.ai-bt.com/si.php on line 10 Synthesis and evaluation of multivalent branched HPMA copolymer-Fab' conjugates targeted to the B-cell antigen CD20.

Literature DB >> 19154157

Synthesis and evaluation of multivalent branched HPMA copolymer-Fab' conjugates targeted to the B-cell antigen CD20.

Russell N Johnson¹, Pavla Kopecková, Jindrich Kopecek.

Abstract

Several drug delivery designs combine synthetic drug carriers with covalently conjugated targeting moieties. Such modifications of monoclonal antibodies (mAb), or their Fab' fragments, inevitably result in diminished affinity for their targeted tissue. In an attempt to overcome this limitation, 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. Evaluation of a multivalent effect was done by determining the apparent K(D) at low concentrations of conjugates, the Sips heterogeneity factor, a, and the binding enhancement factors of each construct. The results clearly indicated that multivalency could improve the affinity of the HPMA copolymer-Fab' conjugates to that of unconjugated mAb.

Entities: CellLine Chemical Disease Gene Species

Mesh：

Substances：

Year: 2009 PMID： 19154157 PMCID： PMC3136133 DOI： 10.1021/bc800351m

Source DB: PubMed Journal: Bioconjug Chem ISSN： 1043-1802 Impact factor: 4.774

54 in total

Review 1. CD20-mediated apoptosis: signalling through lipid rafts.

Authors: Julie P Deans; Haidong Li; Maria J Polyak
Journal: Immunology Date: 2002-10 Impact factor: 7.397

2. Intracellular accumulation of the anti-CD20 antibody 1F5 in B-lymphoma cells.

Authors: Rosana B Michel; M Jules Mattes
Journal: Clin Cancer Res Date: 2002-08 Impact factor: 12.531

3. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene.

Authors: Guillaume Cartron; Laurent Dacheux; Gilles Salles; Philippe Solal-Celigny; Pierre Bardos; Philippe Colombat; Hervé Watier
Journal: Blood Date: 2002-02-01 Impact factor: 22.113

4. Expression of a supramolecular complex at a multivalent interface.

Authors: Olga Crespo-Biel; Choon Woo Lim; Bart Jan Ravoo; David N Reinhoudt; Jurriaan Huskens
Journal: J Am Chem Soc Date: 2006-12-27 Impact factor: 15.419

5. Binding to CD20 by anti-B1 antibody or F(ab')(2) is sufficient for induction of apoptosis in B-cell lines.

Authors: Pina M Cardarelli; Maire Quinn; Dana Buckman; Yu Fang; David Colcher; David J King; Christopher Bebbington; Geoffrey Yarranton
Journal: Cancer Immunol Immunother Date: 2001-12-18 Impact factor: 6.968

6. Effect of shape, size, and valency of multivalent mannosides on their binding properties to phytohemagglutinins.

Authors: R Roy; D Pagé; S F Perez; V V Bencomo
Journal: Glycoconj J Date: 1998-03 Impact factor: 2.916

7. Preparation of Fab' from murine IgG2a for thiol reactive conjugation.

Authors: K D Fowers; J Callahan; P Byron; J I Kopecek
Journal: J Drug Target Date: 2001 Impact factor: 5.121

8. High-molecular weight HPMA copolymer-adriamycin conjugates.

Authors: M Dvorák; P Kopecková; J Kopecek
Journal: J Control Release Date: 1999-08-05 Impact factor: 9.776

9. Alanine-170 and proline-172 are critical determinants for extracellular CD20 epitopes; heterogeneity in the fine specificity of CD20 monoclonal antibodies is defined by additional requirements imposed by both amino acid sequence and quaternary structure.

Authors: Maria J Polyak; Julie P Deans
Journal: Blood Date: 2002-05-01 Impact factor: 22.113

10. Biocompatibility of N-(2-hydroxypropyl) methacrylamide copolymers containing adriamycin. Immunogenicity, and effect on haematopoietic stem cells in bone marrow in vivo and mouse splenocytes and human peripheral blood lymphocytes in vitro.

Authors: B Rihova; M Bilej; V Vetvicka; K Ulbrich; J Strohalm; J Kopecek; R Duncan
Journal: Biomaterials Date: 1989-07 Impact factor: 12.479

27 in total

1. Biological activity of anti-CD20 multivalent HPMA copolymer-Fab' conjugates.

Authors: Russell N Johnson; Pavla Kopečková; Jindřich Kopeček
Journal: Biomacromolecules Date: 2012-02-21 Impact factor: 6.988

2. Engineering polymeric aptamers for selective cytotoxicity.

Authors: Liu Yang; Ling Meng; Xiaobing Zhang; Yan Chen; Guizhi Zhu; Haipeng Liu; Xiangling Xiong; Kwame Sefah; Weihong Tan
Journal: J Am Chem Soc Date: 2011-08-05 Impact factor: 15.419

Review 3. Autoimmune therapies targeting costimulation and emerging trends in multivalent therapeutics.

Authors: Chuda Chittasupho; Teruna J Siahaan; Charlotte M Vines; Cory Berkland
Journal: Ther Deliv Date: 2011-07

4. Drug-free macromolecular therapeutics induce apoptosis of patient chronic lymphocytic leukemia cells.

Authors: Te-Wei Chu; Ken M Kosak; Paul J Shami; Jindřich Kopeček
Journal: Drug Deliv Transl Res Date: 2014-12 Impact factor: 4.617

Review 5. Design of smart HPMA copolymer-based nanomedicines.

Authors: Jiyuan Yang; Jindřich Kopeček
Journal: J Control Release Date: 2015-10-03 Impact factor: 9.776

6. In situ growth of a PEG-like polymer from the C terminus of an intein fusion protein improves pharmacokinetics and tumor accumulation.

Authors: Weiping Gao; Wenge Liu; Trine Christensen; Michael R Zalutsky; Ashutosh Chilkoti
Journal: Proc Natl Acad Sci U S A Date: 2010-09-01 Impact factor: 11.205

Review 10. Macromolecular therapeutics.

Authors: Jiyuan Yang; Jindřich Kopeček
Journal: J Control Release Date: 2014-04-18 Impact factor: 9.776