研究報告一種安全有效的抗CD19 CAR T細胞治療
作者：
小柯機器人發布時間：2019/7/8 14:05:41
美國南加州大學Si-Yi Chen研究組研製了一種安全有效的抗CD19 CAR T細胞治療方法。 2019年6月出版的《Nature Medicine》發表了這項成果。
該團隊合成了一種新的抗CD19 CAR分子（CD19-BBz（86）），該分子來源於攜帶共刺激4-1BB和CD3ζ結構域的CD19-BBz原型。該課題組發現CD19-BBz(86)CAR T細胞產生低水平的細胞因子,表達高水平的凋亡分子並且擴散速度低於原型CD19-BBz CAR T細胞,儘管他們保留有效的溶細胞的活動。課題組人員對患有B細胞淋巴瘤的患者（ClinicalTrials.gov標識符NCT02842138）進行了CD19-BBz（86）CAR T細胞療法的1期試驗。11例中有6例完全緩解的(54.5%)，每例接受一個劑量的2 ×108 - 4 ×108 CD19-BBz(86)CART細胞。值得注意的是，在接受治療的25例患者中，沒有發生神經毒性或CRS(大於1級)。在接受CAR T細胞輸注治療的患者中，包括完全緩解的患者，血清細胞因子水平沒有顯著升高。CD19-BBz(86) CAR T細胞在體內持續增殖分化為記憶細胞。因此，使用新的CD19-BBz(86) CAR T細胞治療產生了一個強有力的和持久的抗淋巴瘤反應，而不會引起神經毒性或嚴重的CRS，代表了一個安全有效的抗CD19 CAR T細胞治療。
據了解，抗CD19嵌合抗原受體（CAR）T細胞療法可以導致嚴重的細胞因子釋放症候群（CRS）和神經毒性，阻礙其治療應用。
附：英文原文
Title: A safe and potent anti-CD19 CAR T cell therapy
Author: Zhitao Ying, Xue F. Huang, Xiaoyu Xiang, Yanling Liu, Xi Kang, Yuqin Song, Xiaokai Guo, Hanzhi Liu, Ning Ding, Tingting Zhang, Panpan Duan, Yufu Lin, Wen Zheng, Xiaopei Wang, Ningjing Lin, Meifeng Tu, Yan Xie, Chen Zhang, Weiping Liu, Lijuan Deng, Shunyu Gao, Lingyan Ping, Xuejuan Wang, Nina Zhou, Junqing Zhang, Yulong Wang, Songfeng Lin, Mierzhati Mamuti, Xueyun Yu, Lizhu Fang, Shuai Wang, Haifeng Song, Guan Wang, Lindsey Jones, Jun Zhu, Si-Yi Chen
Issue&Volume: Volume 25 Issue 6，June 2019
Abstract: Anti-CD19 chimeric antigen receptor (CAR) T cell therapies can cause severe cytokine-release syndrome (CRS) and neurotoxicity, impeding their therapeutic application. Here we generated a new anti-CD19 CAR molecule (CD19-BBz(86)) derived from the CD19-BBz prototype bearing co-stimulatory 4-1BB and CD3ζ domains. We found that CD19-BBz(86) CAR T cells produced lower levels of cytokines, expressed higher levels of antiapoptotic molecules and proliferated more slowly than the prototype CD19-BBz CAR T cells, although they retained potent cytolytic activity. We performed a phase 1 trial of CD19-BBz(86) CAR T cell therapy in patients with B cell lymphoma (ClinicalTrials.gov identifier NCT02842138). Complete remission occurred in 6 of 11 patients (54.5%) who each received a dose of 2×108–4×108 CD19-BBz(86) CAR T cells. Notably, no neurological toxicity or CRS (greater than grade 1) occurred in any of the 25 patients treated. No significant elevation in serum cytokine levels after CAR T cell infusion was detected in the patients treated, including in those who achieved complete remission. CD19-BBz(86) CAR T cells persistently proliferated and differentiated into memory cells in vivo. Thus, therapy with the new CD19-BBz(86) CAR T cells produces a potent and durable antilymphoma response without causing neurotoxicity or severe CRS, representing a safe and potent anti-CD19 CAR T cell therapy.
DOI: 10.1038/s41591-019-0421-7
Source: https://www.nature.com/articles/s41591-019-0421-7