Cytokine release assessment:a good de-risk approach to bi-specific T-cell engagers in non-clinical development / 中国药理学与毒理学杂志

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.

Clinical Research on Detecting the Serum Amyloid A Level of Pregnant Woman in Early Primary Unexplained Recurrent Spontaneous Abortion / 现代检验医学杂志

Objective To research the serum amyloid A(SAA)levels of primary unexplained recurrent early pregnancy loss (REPL),and discuss the viability of regarding the SAA as a independent indicator of REPL.Methods A prospective study was conducted among 96 women with missed spontaneous abortion at Baoji Maternal and Child Care Hospital from January to December 2014.A control group was formed of pregnant women with no history of REPL.Serum samples of both groups were collected to measure SAA levels by enzyme linked immunosorbent assay.The association between SAA and primary unexplained REPL were analyzed according to the multiple factors Logistic models,and the diagnostic value of SAA to RE-PL were detected through receiver operating characteristic.Results Median SAA level was significantly higher among women with REPL(50 μg/ml,interquartile range 26.0~69.0 μg/ml),than that in the control group(11.6 μg/ml,inter-quartile range 6.2~15.5 μg/ml,P=0.000<0.01).The diagnose value of SAA to REPL was perfect good(AUC=0.91), and the most accurate value was 18 μg/ml.The SAA level was an independent indicator of primary unexplained REPL,after adjusting for maternal age and gestational age(OR:1.12,P=0.000).Conclusion Elevated SAA levels found among women with primary unexplained REPL could represent a novel biomarker for this complication of pregnancy.