High-Content Screening Assay for the Identification of Antibody-Dependent Cellular Cytotoxicity Modifying Compounds

Eliza Guti; &#193;kos M&#225;t&#233; Bede; Csongor V&#225;r&#243;czy; Csaba Heged&#369;s; M&#225;t&#233; &#193;. Dem&#233;ny; L&#225;szl&#243; Vir&#225;g

doi:10.3791/64485

JoVE Journal
Cancer Research
Author Produced

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JoVE Journal Cancer Research

High-Content Screening Assay for the Identification of Antibody-Dependent Cellular Cytotoxicity Modifying Compounds

用于鉴定抗体依赖性细胞毒性修饰化合物的高内涵筛选检测

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13:59 min

August 18, 2023

DOI: 10.3791/64485-v

Eliza Guti*^1,2, Ákos Máté Bede*^1,3, Csongor Váróczy*^1,3, Csaba Hegedűs¹, Máté Á. Demény^1,4, László Virág^1,4

¹Department of Medical Chemistry, Faculty of Medicine,University of Debrecen, ²Doctoral School of Molecular Medicine,University of Debrecen, ³National Academy of Scientist Education,University of Debrecen, ⁴ELKH-DE Cell Biology and Signaling Research Group

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该协议提供了一种自动化的、基于图像的高通量技术，用于在存在治疗性抗 HER-2 抗体的情况下鉴定调节自然杀伤细胞介导的乳腺癌细胞杀伤的化合物。

抗体依赖性细胞毒性，简称ADCC，可以由自然杀伤细胞介导，我们称之为NK细胞，粒细胞和巨噬细胞。这些是ADCC的效应细胞。如果靶向表皮生长因子受体HER2的抗体如曲妥珠单抗与肿瘤细胞结合，则这些效应细胞使用其FcyR受体结合抗体的恒定FC区域。

抗体桥接肿瘤细胞和携带FcyR受体的效应细胞，触发其细胞毒性颗粒的释放。这导致癌细胞凋亡。ADCC可能对曲妥珠单抗抗增殖作用无反应的肿瘤有效。

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