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Blood:接种疫苗可增强靶向胞内致癌WT1的CAR-T细胞的抗肿瘤效果!

2018-07-26 MedSci MedSci原创

近期,嵌合抗原受体(CAR)-T细胞治疗血液恶性肿瘤的成功,为进一步开发治疗液体和固体肿瘤的疗法提供了支持。但是,因需要保护正常细胞,CAR-T细胞疗法的扩展受肿瘤表面特异性抗原的可用性限制。虽然细胞内表达多种蛋白,含有大量的肿瘤抗原,但目前和传统的CAR-T细胞均不能以其为靶点。而且,适应性移植的T细胞常出现衰竭和扩展不足,部分是由于机体的免疫抑制。因此,我们需要开发新的方法来进一步激活扩增体内

近期,嵌合抗原受体(CAR)-T细胞治疗血液恶性肿瘤的成功,为进一步开发治疗液体和固体肿瘤的疗法提供了支持。但是,因需要保护正常细胞,CAR-T细胞疗法的扩展受肿瘤表面特异性抗原的可用性限制。

虽然细胞内表达多种蛋白,含有大量的肿瘤抗原,但目前和传统的CAR-T细胞均不能以其为靶点。而且,适应性移植的T细胞常出现衰竭和扩展不足,部分是由于机体的免疫抑制。因此,我们需要开发新的方法来进一步激活扩增体内的CAR-T细胞。

Wilms肿瘤1(WT1)是一种细胞内的致癌性转录因子,在多种白血病和固体肿瘤中过表达,而在正常成人组织中低表达,因此,WT1极有可能作为癌症免疫疗法的靶点。Yasushi Akahori等人开发了一种包含特异性针对WT1235-243/HLA-A*2402复合物的scFv的CAR-T细胞。Yasushi Akahori等人在移植瘤模型中证实了其CAR-T细胞的治疗效果,而且,其效果可通过接种相同抗原的DCs疫苗得到增强。该增强的疗效,至少在一部分上,是通过CAR-T细胞激活扩增来介导的。

Yasushi Akahori等人的研究不仅展现了增加CAR-T细胞靶点的潜力,还提供了一种概念证明,即接种疫苗可提高针对肽/MHC的CAR-T细胞的疗效。

原始出处:

Yasushi Akahori, et al. Anti-tumor activity of CAR-T cells targeting the intracellular oncoprotein WT1 can be enhanced by vaccination. Blood 2018  :blood-2017-08-802926;  doi: https://doi.org/10.1182/blood-2017-08-802926

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    2019-03-22 闆锋旦
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    2019-06-11 仁心济世
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    2018-07-28 jambiya
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    2018-07-27 kafei

    学习了谢谢

    0

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    2018-07-27 CHANGE

    疗效只是效果的众多方面之一,还要看对患者的获益,包括生活质量等因素共同决定效果的

    0

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