让发展中的CAR-T细胞技术平台进入更快的发展

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Shifting the Evolving CAR T Cell Platform into Higher Gear

In this issue of Cancer Cell, Zhao and colleagues test various chimeric antigen receptor (CAR) T cells to show that CD28-CD3z CAR T cells that constitutively express 4-1BBL promote T cell expansion and tumor eradication while reducing exhaustion. The results have important implications for the development of effective CAR T cell therapies in cancer patients.

(A) Examples of enhancing features for T cell-based cancer immunotherapy with corresponding secondgeneration chimeric antigen receptors (CARs), known surface ligands, and potential surface ligands that might enhance these key attributes to maximize CAR T cell efficacy. Highlighted in red is the suggested combination of CAR and surface ligand to maximize CAR T cell efficacy as modeled by Zhao et al. (2015).

(B) A model representing a CD4+ 1928z-41BBL CAR T cell and its potential interaction partners in the tumor microenvironment based on previous work. This T cell shows the combined benefits of 4-1BB and CD28 costimulation while also having emergent features such as specific cytokine and transc**tion factor upregulation. A potential interacting cell population, Tregs, is also represented that can produce suppressive cytokines and thus alter the trans effects of 4-1BBL expression.

让发展中的CAR-T细胞技术平台进入更快的发展

在本期的癌细胞杂志中，赵和他的同事们测试了各种不同的CAR-T细胞，表明了CD28-CD3z CAR T能够持续的表达4-1BBL，增强了T细胞的增殖和肿瘤的杀伤作用，并且能够减少T细胞的衰亡。这个结果展现了在癌症病人的治疗中，高效的CAR-T细胞技术的发展。

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（A）使用相应的二代嵌合抗原受体修饰的T细胞为基础的肿瘤免疫治疗特点增强的例子，已知的表面配体、潜在的表面配位体可能会提高这些关键的属性，以最大限度地提高CAR-T的效能。突出的红色是建议的组合的CAR和表面配位体，以最大限度地提高CAR-T的效能，如由赵设计的（2015）。

（B）一个模型，代表一个CD4+ 1928z-41BBL CAR-T细胞，在之前的工作中发现的它在肿瘤微环境中潜在的相互作用。这个T细胞展示了4-1BB 和CD28共**带来的组合效益，同时也会带来特异性细胞因子和转录因子表达上调。一个潜在的相互作用的细胞群，调节性T细胞，还能够表达抑制性细胞因子，从而改变4-1BBL表达的反式作用。