Characterization of in vitro antibody-dependent cell-mediated cytotoxicity activity of therapeutic antibodies - Impact of effector cells
Characterization of in vitro antibody-dependent cell-mediated cytotoxicity activity of therapeutic antibodies - Impact of effector cells
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DOI：
10.1016/j.jim.2014.03.021
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发表时间：
2014-05-01
影响因子：
2.2
通讯作者：
Song, An
中科院分区：
文献类型：
--
作者：
Chung, Shan;Lin, Yuwen L.;Song, An
抗体依赖性细胞介导的细胞毒性（ADCC）是一种重要的作用机制，与多种治疗性抗体的临床功效有关。常规进行体外 ADCC 测定，使用能够诱导抗体结合的靶细胞裂解的效应细胞，以支持治疗性抗体的研究和开发。 ADCC 检测通常使用外周血单核细胞 (PBMC)、自然杀伤 (NK) 细胞或工程细胞系作为效应细胞进行。在本研究中，我们评估了不同效应细胞类型（包括原代 PBMC、原代 NK 细胞、工程化 NK 细胞系和工程化报告细胞系）对人源化 IgG1 抗体两种糖型的体外 ADCC 活性的影响。这项研究的结果表明，不同效应细胞对抗体的功效和效力有不同的影响，并且发现 CD16a 的同种异型和表达水平都会影响 ADCC 测定中效应细胞的效力。我们的结果还表明，与体外 ADCC 测定的初级效应细胞相比，工程化 NK 或报告细胞系的变异性降低。 (C) 2014 Elsevier B.V. 保留所有权利。
Antibody-dependent cell-mediated cytotoxicity (ADCC) is an important mechanism of action implicated in the clinical efficacy of several therapeutic antibodies. In vitro ADCC assays employing effector cells capable of inducing lysis of target cells bound by antibodies are routinely performed to support the research and development of therapeutic antibodies. ADCC assays are commonly performed using peripheral blood mononuclear cells (PBMCs), natural killer (NK) cells or engineered cell lines as effector cells. In this study we evaluated the impact of different effector cell types including primary PBMCs, primary NK cells, engineered NK cell lines, and an engineered reporter cell line, on the in vitro ADCC activity of two glycoforms of a humanized IgG1 antibody. The results of this study show the differential effects on both the efficacy and potency of the antibodies by different effector cells and the finding that both the allotype and the expression level of CD16a affect the potency of effector cells in ADCC assays. Our results also show that engineered NK or reporter cell lines provide reduced variability compared to primary effector cells for in vitro ADCC assays. (C) 2014 Elsevier B.V. All rights reserved.