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POLYMER CANCEROSTATICS TARGETED BY RECOMBINANT ANTIBODY FRAGMENTS TO GD2-POSITIVE TUMOR CELLS.
Biomacromolecules 2018 November 29
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 anti-tumor 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 non-specific aminolytic reaction with a reactive polymer precursor or via a non-covalent 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 non-covalent polymer-scFv complex proved to be superior to the covalent polymer-scFv conjugate.
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