Polymer Cancerostatics Targeted by Recombinant Antibody Fragments to GD2-Positive Tumor Cells
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Bungarotoxins chemistry MeSH
- 3T3 Cells MeSH
- Doxorubicin administration & dosage chemistry pharmacology MeSH
- Gangliosides immunology MeSH
- Single-Chain Antibodies chemistry immunology MeSH
- Polymethacrylic Acids chemistry MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Nanoconjugates chemistry MeSH
- Cell Proliferation drug effects MeSH
- Antineoplastic Agents administration & dosage chemistry pharmacology MeSH
- Protein Binding MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Bungarotoxins MeSH
- Doxorubicin MeSH
- Duxon MeSH Browser
- ganglioside, GD2 MeSH Browser
- Gangliosides MeSH
- Single-Chain Antibodies MeSH
- Polymethacrylic Acids MeSH
- Nanoconjugates MeSH
- Antineoplastic Agents MeSH
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.
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