Polymer Cancerostatics Targeted by Recombinant Antibody Fragments to GD2-Positive Tumor Cells

Biomacromolecules. 2019 Jan 14;20(1):412-421. doi: 10.1021/acs.biomac.8b01616. Epub 2018 Dec 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Bungarotoxins / chemistry
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Doxorubicin / administration & dosage
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology
  • Gangliosides / immunology*
  • Mice
  • Nanoconjugates / chemistry*
  • Polymethacrylic Acids / chemistry
  • Protein Binding
  • Single-Chain Antibodies / chemistry*
  • Single-Chain Antibodies / immunology

Substances

  • Antineoplastic Agents
  • Bungarotoxins
  • Gangliosides
  • Nanoconjugates
  • Polymethacrylic Acids
  • Single-Chain Antibodies
  • Duxon
  • ganglioside, GD2
  • Doxorubicin