
Entire CD3ε, δ, and γ humanized mouse to evaluate human CD3–mediated therapeutics
Author(s) -
Otoya Ueda,
Naoko Wada,
Yasuko Kinoshita,
Hiroshi Hino,
Mami Kakefuda,
Tsuneo Ito,
Etsuko Fujii,
Mitsuho Noguchi,
Kiyoharu Sato,
Masahiro Morita,
Hiromi Tateishi,
Kaoru Matsumoto,
Chisato Goto,
Yoshiaki Kawase,
Atsuhiko Kato,
Kunihiro Hattori,
Jun-ichi Nezu,
Takahiro Ishiguro,
Kou-ichi Jishage
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep45839
Subject(s) - cd3 , humanized mouse , monoclonal antibody , immune system , immunotherapy , antibody , t cell , antigen , immunology , cancer research , biology , cd8
T cell–mediated immunotherapy is an attractive strategy for treatment in various disease areas. In this therapeutic approach, the CD3 complex is one of the key molecules to modulate T cell functions; however, in many cases, we cannot evaluate the drug candidates in animal experiments because the therapeutics, usually monoclonal antibodies specific to human CD3, cannot react to mouse endogenous Cd3. Although immunodeficient mice transfused with human hematopoietic stem or precursor cells, known as humanized mice, are available for these studies, mice humanized in this manner are not completely immune competent. In this study we have succeeded in establishing a novel mouse strain in which all the three components of the Cd3 complex — Cd3ε, Cd3δ, and Cd3γ — are replaced by their human counterparts, CD3E, CD3D, and CD3G. Basic immunological assessments have confirmed that this strain of human CD3 EDG –replaced mice are entirely immune competent, and we have also demonstrated that a bispecific antibody that simultaneously binds to human CD3 and a tumor-associated antigen (e.g. ERBB2 or GPC3) can be evaluated in human CD3 EDG –replaced mice engrafted with tumors. Our mouse model provides a novel means to evaluate the in vivo efficacy of human CD3–mediated therapy.