Cytokine release assessment:a good de-risk approach to bi-specific T-cell engagers in non-clinical development
10.3867/j.issn.1000-3002.2021.07.006
- VernacularTitle:细胞因子释放风险潜能评估:一种降低双特异性T细胞接合物在非临床研发中风险的良好手段
- Author:
Jin XIE
1
;
Hong-Feng ZHANG
;
Hua-Chun LIU
;
Xin-Hong PAN
;
DAI RENKE
Author Information
1. 广州市疾病预防控制中心,广东广州 510440
- Keywords:
bi-specific T-cell engagers;
single-chain of variable fragments;
cytokine release syndrome
- From:
Chinese Journal of Pharmacology and Toxicology
2021;35(7):522-530
- CountryChina
- Language:Chinese
-
Abstract:
Bi-specific T-cell engagers (BiTEs) show great clinical outcomes for anti-cancer purposes. However, potential cytokine release syndrome (CRS) is notorious to all BiTEs. The mechanism underlying CRS is still not fully known, even though such toxicities are considered to be cytokine release related. Assessment of CRS is a key to non-clinical de-risk programs for BiTEs therapeutic development. In the present review, possible mechanisms are discussed, especially factors contributing to CRS develop?ment. T cell activation may be just an initiation of the CRS cascade, and other cell types can greatly contribute to CRS, such as a chain reaction triggered by downstream B-cells, monocytes, and endothe?lium cells. A non-clinical de-risk program can be designed based on these components in the CRS cascade. Combination of in vitro cytokine release assay, and in vivo mouse and non-human primates studies should be reliable enough to predict and mitigate CRS risk in the clinics. Further more, a good de-risk program should be able to provide ranking for candidates for further development and provide enough confidence to select a first-in-human dose.
