The synthesis of amphiphilic polyethyleneimine/calcium phosphate composites for bispecific T-cell engager based immunogene therapy

Biomater Sci. 2018 Feb 27;6(3):633-641. doi: 10.1039/c7bm01143a.

Abstract

Bispecific T-cell engagers (BiTEs) are single chain variable fragments with specific structures, which could connect the surface antigen on cancer cells and CD3 ligands on T cells, and then engage the T cells for cancer immunotherapy. In this report, a novel organic-inorganic hybrid gene delivery system composed of stearic acid modified polyethyleneimine (stPEI) and calcium phosphate (CaP) was used to deliver MC.DNA into cells to express BiTE antibodies. This gene delivery system exhibits high transfection efficiency, long-term effects and low cytotoxicity in vitro. Furthermore, the gene production, anti-IGF1R/CD3 bispecific T-cell engager, exhibited a rapid redirection activity in T cells to induce cancer cell apoptosis. In summary, the results confirmed that stPEI-CaP could be an efficient gene delivery system for BiTE encoding MC.DNA based gene immunotherapy.

MeSH terms

  • CD3 Complex / immunology
  • Calcium Phosphates / adverse effects
  • Calcium Phosphates / chemistry*
  • Cells, Cultured
  • Genetic Therapy / methods
  • HEK293 Cells
  • Hep G2 Cells
  • Humans
  • Immunotherapy / methods
  • Polyethyleneimine / adverse effects
  • Polyethyleneimine / chemistry*
  • Receptor, IGF Type 1 / immunology
  • Single-Chain Antibodies / administration & dosage*
  • Single-Chain Antibodies / genetics
  • Single-Chain Antibodies / immunology
  • Surface-Active Agents / adverse effects
  • Surface-Active Agents / chemistry*
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • Transfection / methods*

Substances

  • CD3 Complex
  • Calcium Phosphates
  • Single-Chain Antibodies
  • Surface-Active Agents
  • Polyethyleneimine
  • calcium phosphate
  • Receptor, IGF Type 1