[關(guān)鍵詞]
[摘要]
嵌合抗原受體T細(xì)胞(CAR-T)療法極大地改變了癌癥的治療前景,細(xì)胞因子釋放綜合征(CRS)是病理性免疫系統(tǒng)激活的嚴(yán)重全身炎癥反應(yīng),也是CAR-T治療過(guò)程中最常見(jiàn)且致命的毒性反應(yīng)。目前CRS機(jī)制尚未完全闡明,臨床前研究的實(shí)驗(yàn)?zāi)P椭饕ó惙N移植免疫缺陷小鼠模型、同源小鼠模型、轉(zhuǎn)基因小鼠模型、人源化小鼠模型和非人靈長(zhǎng)類動(dòng)物模型。由于種屬差異且缺乏體外細(xì)胞模型,臨床前預(yù)測(cè)CAR-T細(xì)胞引起CRS的風(fēng)險(xiǎn)仍是亟待解決的問(wèn)題。從CRS的相關(guān)指導(dǎo)原則及法規(guī)、機(jī)制及臨床前安全性評(píng)價(jià)方法和模型3個(gè)方面對(duì)CAR-T誘發(fā)的CRS進(jìn)行綜述,以期為CAR-T細(xì)胞治療產(chǎn)品的臨床前安全性評(píng)價(jià)策略提供新的思路。
[Key word]
[Abstract]
Chimeric antigen receptor T cell (CAR-T) therapy has greatly changed the prospects of cancer treatment. Cytokines release syndrome (CRS) is a severe systemic inflammatory response caused by pathological immune system activation, and is also the most common and lethal toxicity during CAR-T cell therapy. At present, the mechanism of CRS has not been fully clarified. Preclinical test models mainly include xenograft mouse model, syngeneic mouse model, transgenic mouse model, humanized mouse model and non-human primate animal model. Due to species differences and the lack of in vita cell models, preclinical prediction the risk of CAR-T cell causes CRS is still an urgent problem. This paper reviewed the relevant guidelines and regulations, mechanisms and preclinical safety evaluation methods and models of CRS in order to provide new ideas for preclinical safety evaluation strategies of CAR-T cell therapy products.
[中圖分類號(hào)]
R951
[基金項(xiàng)目]