Biophysical Evaluation of Rhesus Macaque Fc Gamma Receptors Reveals Similar IgG Fc Glycoform Preferences to Human Receptors.
Biophysical Evaluation of Rhesus Macaque Fc Gamma Receptors Reveals Similar IgG Fc Glycoform Preferences to Human Receptors.
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DOI：
10.3389/fimmu.2021.754710
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发表时间：
2021
影响因子：
7.3
通讯作者：
Ackerman ME
中科院分区：
文献类型：
--
作者：
Crowley AR;Osei-Owusu NY;Dekkers G;Gao W;Wuhrer M;Magnani DM;Reimann KA;Pincus SH;Vidarsson G;Ackerman ME
恒河猴是用于评价人单克隆抗体的常见非人灵长类动物模型，人单克隆抗体是效应子功能依赖于Fc区中保守的N-连接聚糖的分子。这种碳水化合物是糖工程工作的目标，旨在通过调节Fcγ受体的亲和力来改变抗体效应子功能。例如，降低总体核心岩藻糖含量是一种这样的策略，其可以通过增加Fc-Fc γRIIIa亲和力来增加抗体介导的细胞毒性。虽然Fc聚糖的位置在猕猴中是保守的，但糖型频率的差异和唾液酸化聚糖物质中替代单糖的使用增加了恒河猴中糖工程人抗体检测的不确定性。使用一组16种人IgG 1糖变体，我们通过表面等离子体共振测量了猕猴Fcγ R对不同糖型的亲和力。我们的研究结果表明，猕猴是一个听话的物种，在其中测试抗体糖工程的影响。
Rhesus macaques are a common non-human primate model used in the evaluation of human monoclonal antibodies, molecules whose effector functions depend on a conserved N-linked glycan in the Fc region. This carbohydrate is a target of glycoengineering efforts aimed at altering antibody effector function by modulating the affinity of Fcγ receptors. For example, a reduction in the overall core fucose content is one such strategy that can increase antibody-mediated cellular cytotoxicity by increasing Fc-FcγRIIIa affinity. While the position of the Fc glycan is conserved in macaques, differences in the frequency of glycoforms and the use of an alternate monosaccharide in sialylated glycan species add a degree of uncertainty to the testing of glycoengineered human antibodies in rhesus macaques. Using a panel of 16 human IgG1 glycovariants, we measured the affinities of macaque FcγRs for differing glycoforms via surface plasmon resonance. Our results suggest that macaques are a tractable species in which to test the effects of antibody glycoengineering.