Improved Detection of in vivo Human NK Cell-Mediated Antibody-Dependent Cellular Cytotoxicity Using a Novel NOG-FcγR-Deficient Human IL-15 Transgenic Mouse

被引：12

作者：

Katano, Ikumi ^{[1
]}

Ito, Ryoji ^{[1
]}

Kawai, Kenji ^{[2
]}

Takahashi, Takeshi ^{[1
]}

机构：

[1] Cent Inst Expt Anim CIEA, Lab Anim Res Dept, Kawasaki, Kanagawa, Japan

[2] Cent Inst Expt Anim CIEA, Pathol Anal Ctr, Kawasaki, Kanagawa, Japan

来源：

FRONTIERS IN IMMUNOLOGY | 2020年 / 11卷

关键词：

humanized mice; NK cell; Fc gamma R; ADCC; mouse innate immunity; MONOCLONAL-ANTIBODIES; IMMUNE-SYSTEM; MICE; MODEL; ENGRAFTMENT; GENERATION; DELETION; BLOOD;

D O I：

10.3389/fimmu.2020.532684

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

We generated an NOD/Shi-scid-IL2R gamma(null) (NOG) mouse deficient for the Fcer1g and Fcgr2b genes (NOG-Fc gamma R-/- mice), in which monocytes/macrophages do not express activating (Fc gamma RI, III, and IV) or inhibitory (Fc gamma RIIB) Fc gamma receptors. Antibody-dependent cellular cytotoxicity (ADCC) by innate immune cells was strongly reduced in this strain. Thus, while the growth of xenogeneic human tumors engrafted in conventional NOG mice was suppressed by innate cells upon specific antibody treatment, such growth inhibition was abrogated in NOG-Fc gamma R-/- mice. Using this novel strain, we further produced NOG-Fc gamma R-/--mice expressing human IL-15 (NOG-Fc gamma R-/--hIL-15 Tg). The mice inherited unique features from each strain, i.e., the long-term sustenance of human natural killer (NK) cells, and the elimination of mouse innate cell-mediated ADCC. As a result, segregation of human NK cell-mediated ADCC from mouse cell-mediated ADCC was possible in the NOG-Fc gamma R-/--hIL-15 Tg mice. Our results suggest that NOG-Fc gamma R-/--hIL-15 Tg mice are useful for validating the in vivo function of antibody drug candidates.

引用

页数：9

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