Polymer cancerostatics targeted by recombinant antibody fragments to GD2-positive tumor cells

0499714 - ÚMCH 2020 RIV US eng J - Journal Article
Pola, Robert - Král, Vlastimil - Filippov, Sergey K. - Kaberov, Leonid I. - Etrych, Tomáš - Sieglová, Irena - Sedláček, Juraj - Fábry, Milan - Pechar, Michal
Polymer cancerostatics targeted by recombinant antibody fragments to GD2-positive tumor cells.
Biomacromolecules. Roč. 20, č. 1 (2019), s. 412-421. ISSN 1525-7797. E-ISSN 1526-4602
R&D Projects: GA ČR(CZ) GA16-17207S; GA MZd(CZ) NV16-28594A; GA MPO FV10312
Institutional support: RVO:61389013 ; RVO:68378050
Keywords : polymer cancerostatics * drug targeting * scFv
OECD category: Polymer science; Biochemical research methods (UMG-J)
Impact factor: 6.092, year: 2019
Method of publishing: Limited access
https://pubs.acs.org/doi/10.1021/acs.biomac.8b01616

A water-soluble polymer cancerostatic actively targeted against cancer cells expressing a disialoganglioside antigen GD2 was designed, synthesized and characterized. A polymer conjugate of an antitumor drug doxorubicin with a N-(2-hydroxypropyl)methacrylamide-based copolymer was specifically targeted against GD2 antigen-positive tumor cells using a recombinant single chain fragment (scFv) of an anti-GD2 monoclonal antibody. The targeting protein ligand was attached to the polymer–drug conjugate either via a covalent bond between the amino groups of the protein using a traditional nonspecific aminolytic reaction with a reactive polymer precursor or via a noncovalent but highly specific interaction between bungarotoxin covalently linked to the polymer and the recombinant scFv modified with a C-terminal bungarotoxin-binding peptide. The GD2 antigen binding activity and GD2-specific cytotoxicity of the targeted noncovalent polymer–scFv complex proved to be superior to the covalent polymer–scFv conjugate.
Permanent Link: http://hdl.handle.net/11104/0292360