期刊
JOURNAL OF IMMUNOLOGY
卷 179, 期 5, 页码 3325-3331出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.179.5.3325
关键词
-
类别
资金
- Medical Research Council [G0600007] Funding Source: Medline
- MRC [G0600007] Funding Source: UKRI
- Medical Research Council [G0600007] Funding Source: researchfish
The CD28-specitic mAb TGN1412 rapidly caused a life-threatening cytokine storm in all six healthy volunteers in the Phase I clinical trial of this superagonist, signaling a failure of preclinical safety testing. We report novel in vitro procedures in which TGN1412, immobilized in various ways, is presented to human white blood cells in a manner that stimulates the striking release of cytokines and profound lymphocyte proliferation that occurred in vivo in humans. The novel procedures would have predicted the toxicity of this superagonist and are now being applied to emerging immunotherapeutics and to other therapeutics that have the potential to act upon the immune system. Data from these novel procedures, along with data from in vitro and in vivo studies in nonhuman primates, suggest that the dose of TGN1412 given to human volunteers was close to the maximum immunostimulatory dose and that TGN1412 is not a superagonistin nonhuman primates.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据