TX99 Is a Neutralizing Monoclonal Antibody Against Mouse TIGIT

Monoclon Antib Immunodiagn Immunother. 2018 Apr;37(2):105-109. doi: 10.1089/mab.2018.0001. Epub 2018 Apr 12.


T cell immunoglobulin and ITIM domains (TIGIT) is an inhibitory immunoreceptor expressed on NK cells, effector and memory T cells, and regulatory T cells (Tregs). The ligands for TIGIT are CD155 (PVR) and CD112 (PVRL2, nectin-2), which are broadly expressed on hematopoietic cells and nonhematopoietic cells. TIGIT negatively regulates antitumor responses, but promotes autoimmune reaction. Although neutralizing anti-human TIGIT mAbs are under clinical trials for cancers, how the blockade of TIGIT interaction with the ligands shows tumor immunity still remains unclear. Although analyses of mouse tumor model using a neutralizing anti-mouse TIGIT (mTIGIT) mAbs should be useful to address this issue, there are limitations to this type of studies due to unavailability of neutralizing anti-mTIGIT mAbs. In this study, we generated five clones of anti-mTIGIT mAbs, designated TX99, TX100, TX103, TX104, and TX105. We show that TX99 and TX100 showed the strongest binding to TIGIT. We also show that TX99 interfered with the interaction between TIGIT and CD155 and increased NK cell-mediated cytotoxicity against CD155-expressing RMA-S cells. Thus, TX99 is a unique neutralizing mAb that can be used for studies of mTIGIT functions.

Keywords: NK cells; TIGIT; blocking antibodies.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / biosynthesis
  • Antibodies, Monoclonal / isolation & purification
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Neutralizing / biosynthesis
  • Antibodies, Neutralizing / isolation & purification
  • Antibodies, Neutralizing / pharmacology*
  • Binding Sites, Antibody
  • Cell Line, Tumor
  • Clone Cells
  • Coculture Techniques
  • Cytotoxicity, Immunologic / drug effects*
  • Gene Expression
  • Humans
  • Hybridomas / chemistry
  • Hybridomas / immunology
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology
  • Ligands
  • Mice
  • Mice, Inbred C57BL
  • Protein Binding
  • Rats
  • Rats, Wistar
  • Receptors, Immunologic / genetics*
  • Receptors, Immunologic / immunology
  • Receptors, Virus / genetics*
  • Receptors, Virus / immunology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Ligands
  • Receptors, Immunologic
  • Receptors, Virus
  • Recombinant Fusion Proteins
  • T cell Ig and ITIM domain protein, mouse
  • poliovirus receptor