Development and Characterization of Novel Monoclonal Antibodies Against Human DNAM-1

Monoclon Antib Immunodiagn Immunother. 2017 Jun;36(3):135-139. doi: 10.1089/mab.2016.0049. Epub 2017 May 12.


DNAM-1 (CD226) is an activating immunoreceptor expressed on lymphocytes and myeloid cells. CD155 and CD112 are the ligands for DNAM-1. DNAM-1 plays an important role in tumor immunity mediated by CD8+ T cells and NK cells. Moreover, the interaction of DNAM-1 with the ligands contributed to the development of acute graft versus host disease (GVHD) and treatment with anti-DNAM-1 monoclonal antibodies (mAb) dramatically improved acute GVHD in a mouse model, suggesting that DNAM-1 may be a good molecular target for therapy to acute GVHD in human. In this study, we generated and characterized five novel clones of anti-human DNAM-1 mAbs, named TX94, TX95, TX96, TX107, and TX108. Among these mAbs, TX94 is a unique neutralizing mAb that most efficiently blocked the interaction between DNAM-1 and CD155. Furthermore, TX94 inhibited NK cell-mediated cytotoxicity against a tumor cell line and suppressed CD8+ T cell proliferation mediated by allogeneic mixed lymphocyte reaction. Thus, TX94 may be useful for molecular therapy targeting DNAM-1.

Keywords: CD8+ T cells; DNAM-1; NK cells; blocking antibodies.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / biosynthesis*
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Neutralizing / biosynthesis*
  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / pharmacology
  • Antibody Specificity
  • Antigens, Differentiation, T-Lymphocyte / chemistry
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Proliferation
  • Cells, Cultured
  • Cytotoxicity, Immunologic / drug effects
  • Gene Expression
  • Humans
  • Immunoglobulin Fc Fragments / chemistry
  • Immunoglobulin Fc Fragments / genetics
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Lymphocyte Culture Test, Mixed
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Protein Binding
  • Receptors, Virus / antagonists & inhibitors
  • Receptors, Virus / chemistry
  • Receptors, Virus / genetics
  • Receptors, Virus / immunology*
  • Recombinant Fusion Proteins / biosynthesis*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / pharmacology


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antigens, Differentiation, T-Lymphocyte
  • CD226 antigen
  • Immunoglobulin Fc Fragments
  • Receptors, Virus
  • Recombinant Fusion Proteins
  • poliovirus receptor