肿瘤细胞治疗研究
英文原题：Therapeutic T cells with 3-in-1 strategy for the treatment of biliary tract cancer.
Therapeutic T cells with 3-in-1 strategy for the treatment of biliary tract cancer.
临床上，10例晚期胆道癌（BTC）患者接受ScTILs治疗；
肿瘤T细胞疗法面临多种障碍，包括抗原表达异质性、肿瘤微环境不利以及T细胞扩增有限。我们采用‘三合一’策略制备超循环TIL样细胞（ScTIL）：以增强型受体（ER，即PD-1与CD28融合蛋白）修饰PD-1阳性外周血T细胞，以逆转抑制信号，并加入抗CD19嵌合抗原受体（CAR）促进扩增（CFE）。ScTIL在体内外均能有效杀伤肿瘤细胞。临床上，10例晚期胆道癌（BTC）患者接受ScTIL治疗；事后分析显示，在剂量适宜或B细胞正常的患者组（5/10）中，ScTIL单药治疗的总生存期（OS）中位数为18.3个月，优于BTC一线治疗（OS 12个月）。该方案无需化疗预处理和白细胞介素-2（IL-2），安全性较好，不依赖手术获取材料，生产周期也更短。总体而言，ScTIL有望成为未来BTC治疗的一种选择。本研究已在中国临床试验注册中心登记（ChiCTR2000029738）。
T cell therapy for tumors faces barriers like heterogeneous antigen expression, an unfriendly tumor microenvironment, and limited T cell expansion. We adopt a 3-in-1 strategy to produce super circulating TIL-like (tumor-infiltrating lymphocyte-like) cells (ScTILs): modifying PD-1-positive peripheral blood T cells with an enhance receptor (ER), a PD-1 and CD28 fusion protein to reverse inhibitory signal, and an anti-CD19 chimeric antigen receptor (CAR) for expansion (CFE). ScTILs kill tumor cells effectively in vitro and in vivo. Clinically, ten advanced biliary tract cancer (BTC) patients receive ScTILs treatment; post hoc analysis shows that ScTILs monotherapy yields a median overall survival (OS) of 18.3 months in appropriate dose or normal B cell groups (5/10), outperforming first-line BTC treatment (OS 12 months). It skips chemo-pre-treatment and interleukin-2 (IL-2), with better safety, no reliance on surgical materials, and a shorter production cycle. Overall, ScTILs are a promising therapy for future BTC treatment. This study is registered with ChiCTR (ChiCTR2000029738).
MEMBER ACCOUNT
登录成功会直接打开下一页。
