Increase in proliferation rate and normalization of TNF-alpha secretion by blockage of gene transfer-induced apoptosis in lymphocytes using low-dose cyclosporine A

Cancer Gene Ther. 2000 Nov;7(11):1411-3. doi: 10.1038/sj.cgt.7700256.

Abstract

Efficient gene transfer of lymphocytes is extremely difficult. We have shown previously that induction of apoptosis may play a role in the gene transfer resistance of lymphocytes. Anti-CD3 antibody can be used as a surrogate for receptor-mediated gene transfer in T lymphocytes. However, anti-CD3 antibody has been shown to be the causative agent of apoptosis in receptor-mediated gene transfer. In this study, we show that blockage of apoptosis by addition of low-dose cyclosporine A can lead to normalization of elevated TNF-alpha secretion and to a significant increase in the proliferation rate of transfected lymphocytes. In contrast, this had no negative effect on cytotoxic activity of immunologic effector cells called cytokine-induced killer cells. Therefore, blockage of apoptosis should have an impact on the use of lymphocytes transfected with cytokine genes as immunologic effector cells in cancer gene therapy protocols.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • CD3 Complex / immunology
  • Cell Division
  • Cells, Cultured
  • Chromium Radioisotopes / metabolism
  • Cyclosporine / therapeutic use*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Gene Transfer Techniques*
  • Genetic Therapy / methods
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Killer Cells, Natural / metabolism
  • Lymphocytes / metabolism
  • Plasmids / metabolism
  • Transfection
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • CD3 Complex
  • Chromium Radioisotopes
  • Immunosuppressive Agents
  • Tumor Necrosis Factor-alpha
  • Cyclosporine