Construction and characterization of a novel fusion protein consisting of anti-CD3 antibody fused to recombinant interleukin-2

Oncol Rep. 2006 May;15(5):1211-6.

Abstract

T cells can be activated in vitro by monoclonal antibodies to CD3 (anti-CD3) to become non-MHC restricted killer cells (CD3-AK). Anti-CD3 activation upregulates the expression of the interleukin (IL)-2 receptors on T cells whose expansion is facilitated by IL-2. The therapeutic effect of in vivo administration of anti-CD3 and IL-2 has been investigated in many types of human cancers. To circumvent the toxicities posed by systemic administration of high-dose IL-2, there is interest in forming a strategy for targeting and concentrating IL-2 at the site where it is needed. This study investigates the feasibility of constructing a novel fusion protein consisting of IL-2 fused to the constant region of anti-CD3 antibody. Our results indicate that the specific IL-2 receptor-binding capability and bioactivity of the IL-2 portion as well as the CD3-binding and biological functions of anti-CD3 portion remain intact in this anti-CD3/IL-2 fusion protein. Thus, cytokines fused to anti-CD3 antibody by genetic engineering is feasible and may provide a new class of immunotherapeutics for cancer.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism*
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • CD3 Complex / immunology*
  • Cytotoxicity, Immunologic
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Flow Cytometry
  • Immunotherapy*
  • Interleukin-2 / metabolism*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C3H
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / therapy*
  • Receptors, Interleukin-2 / metabolism
  • Recombinant Fusion Proteins / therapeutic use*
  • Recombinant Proteins / metabolism
  • T-Lymphocytes / immunology
  • Tumor Cells, Cultured / immunology

Substances

  • Antibodies, Monoclonal
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • Interleukin-2
  • Receptors, Interleukin-2
  • Recombinant Fusion Proteins
  • Recombinant Proteins