以CD7为靶点的“现成”CAR-T在治疗复发和难治性T细胞恶性肿瘤患者中表现出强大的体内扩张能力和高疗效。
CD7 targeted "off-the-shelf" CAR-T demonstrates robust in vivo expansion and high efficacy in the treatment of patients with relapsed and refractory T cell malignancies.
发表日期：2023 Sep 12
作者：
Shiqi Li, Xinxin Wang, Lin Liu, Jia Liu, Jun Rao, Zhongtao Yuan, Li Gao, Yu Li, Le Luo, Gui Li, Zhimin Li, Sheng Li, Jiaping He, Lihua Zhang, Lvzhe Chen, Wenhui Huang, Ping Yin, Chunmin Li, Xiaoping Li, Youcheng Wang, Yancheng Dong, Dingsong Zhang, Qingying Zang, Yingnian Chen, Lianjun Shen, Wenling Li, Wei Cao, Xi Zhang, Sanbin Wang
来源：
LEUKEMIA
摘要：
T-细胞急性淋巴细胞白血病(T-ALL)代表着医疗需求严重不足的领域。一旦复发，患者的治疗选择有限且预后不良。T-ALL抗原如CD7在正常T细胞和自然杀伤(NK)细胞中广泛表达，CAR-T疗法在 T细胞恶性肿瘤方面的成功延伸受到CAR-T细胞自杀、高生产成本和潜在产品污染的挑战。GC027是一种用于T细胞恶性肿瘤的“即开即用”异基因CD7靶向CAR-T治疗产品。在小鼠异种移植模型中，它表现出卓越的细胞扩张和抗白血病效果。在我们之前的研究中，我们观察到使用GC027治疗的前两位复发和难治(R/R)T-ALL患者的有希望的疗效结果。在扩大的研究中，12名患者中有11名在GC027输注后的1个月内迅速清除了T淋巴母细胞，并达到完全缓解。GC027细胞在输注后迅速扩张，并在输注后5-10天左右达到峰值。对于大多数有反应的患者（9/11），在输注后4周内无法通过流式细胞术或实时定量聚合酶链反应(qPCR)检测到GC027。一名患者具有>3年的无进展生存期。GC027具有可管理的毒性谱，相比(R/R)T细胞恶性肿瘤的标准化疗方案，GC027显示出卓越的临床疗效。© 2023. 作者经Springer Nature Limited独家许可。
T-cell acute lymphoblastic leukemia (T-ALL) represents an area of highly unmet medical needs. Once relapsed, patients have limited treatment options and poor prognosis. T-ALL antigens such as CD7 is extensively expressed in normal T cells and natural killer (NK) cells, and extending the success of CAR-T therapy to T cell malignancies was challenged by CAR-T cell fratricide, high production cost, and potential product contaminations. GC027 is an "off-the-shelf" allogeneic CD7 targeted CAR-T therapeutic product for T cell malignancies. It demonstrated superior cell expansion and antileukemia efficacy in mouse xenograft model. In our previous study, we observed promising efficacy results in the first two relapsed and refractory(R/R) T-ALL patients treated with GC027. In the expanded study, 11 out of 12 patients had rapid eradication of T-lymphoblasts and reached complete response within 1-month after GC027 infusion. GC027 cells expanded quickly beginning at infusion and reached to peak around 5-10 days after infusion. For most patients with a response(9/11), GC027 could not be detected via flow cytometry or qPCR 4 weeks after infusion. One patient had progression free survival of >3 years. With manageable toxicity profile, GC027 demonstrated superior clinical efficacy to standard chemotherapy regimens in (R/R) T cell malignancies.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.