用于细胞免疫的嵌合抗原受体：当前理解和未来的发展方向

nhdr123

Chimeric antigen receptors for T cell

immunotherapy: current understandingand

future directions

用于细胞免疫的嵌合抗原受体：当前理解和未来的发展方向

Abstract

Background The genetic engineering of T cells through the introductionof a chimeric antigen receptor (CAR) allows for generation of tumor-targeted Tcells. Once expressed by T cells, CARs combine antigen-specificity with T cell activationin a single fusion molecule. Most CARs are comprised of an antigenbinding domain,an extracellular spacer/hinge region, a trans-membrane domain and anintracellular signaling domain resulting in T cell activation after antigenbinding.

摘要

背景  基因工程通细胞通过CAR的引入，允许有瘤靶点的T细胞传代。T细胞一旦表达，在单融合分子中，CARs结合了T细胞被活化的特异性抗原，绝大多数嵌合抗原受体由一个抗原结合域、一个细胞外隔/铰链区、一个反式薄膜域和一个抗原结合后T细胞活化的胞内信号域组成。

Methods   We performed a search of the literature regarding tumorimmunotherapy  using  CAR-modified T cells to provide a concisereview of this topic.

我们通过搜集关于用改进的嵌合抗原受体T细胞的肿瘤免疫治疗的大量文献去精简这个话题的观点

Results This review aims to focus on theelements of CAR design required for successful application of this technologyin cancer immunotherapy. Most notably, proper target antigen selection,co-stimulatory signaling, and the ability of CAR-modified T cells to traffic,persist and retain function after adoptive transfer are required for optimaltumor eradication. Furthermore, recent clinical trials have demonstrated tumorburden and chemotherapy conditioning before adoptive transfer as beingcritically important for this therapy. Future research into counteracting thesuppressive tumor microenvironment and the ability to activate an endogenousanti-tumor response by CAR-modified T cells may enhance the therapeuticpotential of this treatment.

结果

这篇综述聚焦于CAR设计的原理要求这一科学技术在肿瘤免疫治疗方面的成功应用。最值得注意的是，适当抗原靶点的选择、刺激信号和改进的CAR-T细胞的运作能力，过继转移后的保留功能被认为是最佳的灭瘤。此外，最近的临床试验已经证明在过继转移前的肿瘤负担及化疗调理在治疗中极其重要。对抵消抑制肿瘤微环境和通过改进的CAR-T细胞激活内源性抗肿瘤反应的能力的进一步研究可能会提高这种治疗的治疗潜力。

Conclusions   Inconclusion, CAR-modified T cell therapy is a highly promising treatment forcancer, having already demonstrated both promising preclinical and clinicalresults. However, further modification and additional clinical trials will needto be conducted to ultimately optimize the anti-tumor efficacy of thisapproach.

综上，改进的CAR-T细胞在癌症治疗方面有很好的治疗前景，已经证实有很好的潜伏期和临床效果。然而，需要进行进一步的改良和附加临床试验来优化抗肿瘤的功效。