Anti-JL1 antibody-conjugated poly (L-lysine) for targeted gene delivery to leukemia T cells

J Control Release. 2001 May 14;72(1-3):171-8. doi: 10.1016/s0168-3659(01)00273-5.

Abstract

We have designed the gene delivery carrier targeted to Molt 4 cells, human leukemia T cells, using monoclonal antibody against leukemia-specific JL1 antigen, anti-JL1 antibody, as a targeting moiety. Anti-JL1 antibody has been proven to bind to JL1 antigen and subsequently be internalized into Molt 4 cells, demonstrating that anti-JL1 antibody has the potential as a targeting ligand for leukemia-specific gene transfer. Anti-JL1 antibody was modified with the heterobifunctional crosslinker, PDPH, at carbohydrate sites and conjugated to thiolated poly-L-lysine (PLL) via disulfide bridges. The composition and antigen binding affinity of antibody-PLL conjugates were analyzed by the amino acid analysis and the flow cytometry, respectively. Antibody-PLL conjugates neutralized pSV-beta-galactosidase plasmid DNA at 5:1 weight ratio and condensed into about 200--300-nm complexes. DNA/antibody-PLL complexes were effectively internalized into Molt 4 cells after 4 h incubation at 37 degrees C and showed significantly higher in vitro transfection efficiency than DNA/PLL complexes and DNA/Lipofectin formulation due to the targeting effect of receptor-mediated endocytosis induced by anti-JL1 antibody.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / analysis
  • Antibody Specificity
  • Antigen-Antibody Reactions
  • Antigens, Differentiation, T-Lymphocyte / administration & dosage
  • Antigens, Differentiation, T-Lymphocyte / chemistry*
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • Antimetabolites / therapeutic use
  • Electrophoresis, Agar Gel
  • Flow Cytometry
  • Ganciclovir / therapeutic use
  • Gene Targeting / methods*
  • Genetic Vectors / administration & dosage
  • Humans
  • Leukemia, T-Cell / genetics*
  • Leukemia, T-Cell / immunology*
  • Ligands
  • Light
  • Microscopy, Confocal
  • Plasmids / genetics
  • Polylysine / administration & dosage
  • Polylysine / chemistry*
  • Scattering, Radiation
  • Transfection / methods*
  • Tumor Cells, Cultured

Substances

  • Amino Acids
  • Antigens, Differentiation, T-Lymphocyte
  • Antimetabolites
  • JL1 antigen
  • Ligands
  • Polylysine
  • Ganciclovir