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针对TRKB的新型CAR-T细胞用于治疗固体癌症

Dandan Liang¹, Jie Tang¹, Bin Sun¹

¹Department of Targeting Therapy & Immunology and Laboratory of Animal Tumor Models, Cancer Center and State Key Laboratory of Respiratory Health and Multimorbidity and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Apoptosis : an international journal on programmed cell death

|March 18, 2024

概括

化学抗原受体 (CAR) T细胞疗法向热胺相关激酶受体B (TRKB) 显示出对固体瘤的承诺. 在临床前模型中,CAR-T细胞有效地消除了癌细胞和表达TRKB的癌症干细胞.

科学领域:

免疫治疗是一种免疫疗法.
在瘤学瘤学.
分子生物学分子生物学

背景情况:

化学抗原受体 (CAR) T细胞疗法对血液癌症有效,但对固体瘤未得到充分研究.
热胺相关酶受体B (TRKB) 与固体瘤进展,恶性瘤和耐药性有关.
准TRKB为新型固体瘤治疗提供了一个潜在的战略.

研究的目的:

开发和评估针对固体瘤中TRKB受体的CAR-T细胞疗法.
评估由大脑衍生的神经营养因子 (BDNF) 和神经营养因子4 (NTF4) 基CAR-T细胞对表达TRKB的癌症的疗效.
研究针对TRKB的CAR-T细胞在治疗肝细胞癌和胰腺癌方面的潜力.

主要方法:

对基于BDNF和NTF4的CAR-T细胞进行TRKB受体向查.
在实验室中评估CAR-T细胞对表达TRKB的癌细胞系和癌症干细胞 (CSC) 的细胞毒性.
在体内评估CAR-T细胞在抑制小鼠肝细胞癌异种移植瘤生长中的疗效.

主要成果:

在肝细胞癌和胰腺癌细胞系中,TRKB过度表达,包括CSCs.
在BDNF-CAR T细胞和NTF4-CAR T细胞中,TRKB表达性癌细胞和CSCs的剂量依赖性杀死得到证明.
与BDNF-CAR T细胞相比,NTF4-CAR T细胞在体内表现出更好的肝细胞癌异种移植生长抑制.

结论:

针对TRKB的CAR-T细胞疗法是治疗侵袭性固体瘤的有希望的策略.
基于BDNF和NTF4的CAR-T细胞对表达TRKB的癌症和CSCs表现出强大的抗瘤活性.
针对TRKB的CAR-T细胞的进一步开发可能会为患有固体癌症的患者带来新的治疗选择.

关键词:

这就是为什么BDNF是BDNF.在CART-T中,我们可以使用CAR-T.癌症干细胞是癌症干细胞.肝癌是一种肝癌.没有NTF4的胰腺癌是一种胰腺癌.这就是TRKBB.

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