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

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
Genki OkumuraKazuko Shibuya

Abstract

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.

References

Aug 13, 2003·The Journal of Experimental Medicine·Cristina BottinoAlessandro Moretta
Mar 9, 2005·Biochemical and Biophysical Research Communications·Satoko Tahara-HanaokaAkira Shibuya
Jul 29, 2008·Molecular Immunology·Dirk H J VerhoevenArjan C Lankester
Nov 26, 2008·The Journal of Experimental Medicine·Akiko Iguchi-ManakaAkira Shibuya
Oct 13, 2010·Proceedings of the National Academy of Sciences of the United States of America·Tsukasa NabekuraAkira Shibuya
Apr 23, 2013·Monoclonal Antibodies in Immunodiagnosis and Immunotherapy·Yumi YamashitaKazuko Shibuya

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Citations

Nov 30, 2019·Cytometry. Part B, Clinical Cytometry·Yuko Nagayama-HasegawaKazuko Shibuya
Apr 27, 2021·Monoclonal Antibodies in Immunodiagnosis and Immunotherapy·Yumi Yamashita-KanemaruAkira Shibuya

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Methods Mentioned

BETA
flow cytometry

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