Thaventhiran Thilipan, Wong Wai, Alghanem Ahmad F, Alhumeed Naif, Aljasir Mohammad A, Ramsey Simeon, Sethu Swaminathan, Yeang Han Xian Aw, Chadwick Amy E, Cross Michael, Webb Steven D, Djouhri Laiche, Ball Christina, Stebbings Richard, Sathish Jean G
1 Medical Research Council Centre for Drug Safety Science and Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom.
2 Inflammation and Remodeling, Pfizer Research Unit, Cambridge, Massachusetts.
Monoclon Antib Immunodiagn Immunother. 2019 Apr;38(2):60-69. doi: 10.1089/mab.2018.0042.
CD28 superagonist (CD28SA), a therapeutic immunomodulatory monoclonal antibody triggered rapid and exaggerated activation of CD4 effector memory T cells (T) in humans with unwanted serious adverse effects. It is well known that distinct metabolic programs determine the fate and responses of immune cells. In this study, we show that human CD4 T stimulated with CD28SA adopt a metabolic program similar to those of tumor cells with enhanced glucose utilization, lipid biosynthesis, and proliferation in hypoxic conditions. Identification of metabolic profiles underlying hyperactive T cell activation would provide a platform to test safety of immunostimulatory antibodies.
CD28超激动剂(CD28SA)是一种治疗性免疫调节单克隆抗体,可在人体中引发CD4效应记忆T细胞(T细胞)的快速且过度激活,并产生不良的严重副作用。众所周知,不同的代谢程序决定了免疫细胞的命运和反应。在本研究中,我们发现用CD28SA刺激的人类CD4 T细胞采用了类似于肿瘤细胞的代谢程序,在缺氧条件下增强了葡萄糖利用、脂质生物合成和增殖。确定过度活跃的T细胞激活背后的代谢谱将为测试免疫刺激抗体的安全性提供一个平台。