In vivo assay of human NK-dependent ADCC using NOD/SCID/γcnull (NOG) mice
In vivo assay of human NK-dependent ADCC using NOD/SCID/γcnull (NOG) mice
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DOI：
10.1016/j.bbrc.2010.07.145
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发表时间：
2010-09-03
影响因子：
3.1
通讯作者：
Ishii, Naoto
中科院分区：
文献类型：
--
作者：
Shiokawa, Miho;Takahashi, Takeshi;Ishii, Naoto
单克隆抗体对于分子靶向治疗的成功至关重要。最近，已经开发了许多治疗性抗体用于各种疾病，包括癌症和自身免疫性疾病。迫切需要有效评估这些候选抗体的实验系统。抗体用于杀死肿瘤细胞的机制之一是抗体依赖性细胞毒性（ADCC），其中自然杀伤细胞（NK）是主要介导者。诱导ADCC的能力通常在人-小鼠异种移植物模型中评估，其中将含有NK细胞沿着抗体的人外周血单核细胞（PBMC）给予荷瘤免疫缺陷小鼠。然而，来自其他细胞群体的污染通常会影响肿瘤生长，使得难以评估抗体的效果。在这项研究中，我们建立了一个新的NK依赖性ADCC检测模型，使用超免疫缺陷小鼠，NOD/SCID/γ c（null）（NOG）。我们的模型系统简单地由三个元素组成：分离的人NK细胞，伯基特淋巴瘤细胞系（Daudi）和抗CD 20抗体（利妥昔单抗）。在该实验环境中，当来自健康供体的人NK细胞与利妥昔单抗一起沿着给药时，其保留了其杀伤活性并抑制NOG小鼠中Daudi细胞的生长。因此，该系统可用于评估人NK细胞的体内功能。(C)2010年爱思唯尔公司All rights reserved.
Monoclonal antibodies are essential to the success of molecularly targeted therapies. Recently, numerous therapeutic antibodies have been developed for various diseases, including cancer and autoimmune diseases. Experimental systems to effectively evaluate these candidate antibodies are urgently needed. One of the mechanisms used by antibodies to kill tumor cells is antibody-dependent cellular cytotoxicity (ADCC), in which natural killer cells (NK) are the main mediator. The capacity to induce ADCC has conventionally been assessed in the human-mouse xeno-graft model, in which human peripheral blood mononuclear cells (PBMC), containing NK cells along with antibodies, are administered to tumor-bearing immunodeficient mice. However, contamination from other cellular populations often affects tumor growth, making it difficult to evaluate the antibody's effect. In this study, we established a new NK-dependent ADCC assay model using a supra-immunodeficient strain of mice, NOD/SCID/gamma c(null) (NOG). Our model system simply consisted of three elements: isolated human NK cells, a Burkitt's lymphoma cell line (Daudi), and an anti-CD20 antibody (Rituximab). In this experimental setting, human NK cells from healthy donors retained their killing activity and suppressed the growth of Daudi cells in NOG mice when they were administered along with Rituximab. This system, therefore, is useful for evaluating the in vivo function of human NK cells. (C) 2010 Elsevier Inc. All rights reserved.