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

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

Author information

1
1 Department of Immunology, Faculty of Medicine , Tsukuba, Japan .
2
2 Life Science Center of Tsukuba Advanced Research Alliance (TARA), University of Tsukuba , Tsukuba, Japan .

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.

KEYWORDS:

CD8+ T cells; DNAM-1; NK cells; blocking antibodies

PMID:
28498033
DOI:
10.1089/mab.2016.0049
[Indexed for MEDLINE]

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