靶向巨噬细胞的癌症治疗策略
Macrophage-directed therapeutic strategies in cancer.
肿瘤相关巨噬细胞(TAMs)是肿瘤微环境的主要组成部分,具有显著的功能可塑性,根据所处的微环境信号,既可表现为促进肿瘤进展的免疫抑制细胞,也可表现为支持抗肿瘤免疫的免疫刺激细胞。
英文原题:The Modular CAR: Adapting T Cells without Reengineering Them.
嵌合抗原受体(CAR)T细胞的治疗潜力长期以来一直受到工程化受体静态性质的限制;一旦制造完成,该细胞就固定针对单一抗原,无法应对实体瘤所特有的免疫逃逸和抗原异质性。
嵌合抗原受体(CAR)T 细胞的治疗潜力长期以来受到工程化受体静态特性的限制;一旦制造完成,该细胞即被锁定于单一抗原,无法应对实体瘤所特有的免疫逃逸和抗原异质性。尽管双特异性构建体和逻辑门控回路等解决方案已被提出,但每一种都在制造时向细胞产品中编码了额外的复杂性,且不具备输注后重编程的能力。在本期,Kuo 及其同事报告了一种根本不同的策略——meditope 赋能 CAR,即将一个小型、结构正交的肽对接界面嵌入 CAR 的胞外结构域,从而将固定的细胞产品转化为可编程平台,可通过给予模块化衔接分子对其进行重定向、选择性扩增或精确追踪。参见 Kuo 等人的相关文章,第 XX 页。
The therapeutic potential of chimeric antigen receptor (CAR) T cells has long been limited by the static nature of the engineered receptor; once manufactured, the cell is committed to a single antigen, unable to respond to the immune evasion and antigen heterogeneity that define solid tumors. Although solutions such as bispecific constructs and logic-gated circuits have been proposed, each encodes additional complexity into the cell product at the time of manufacture, with no capacity for post-infusion reprogramming. In this issue, Kuo and colleagues report a fundamentally different strategy-the meditope-enabled CAR-in which a small, structurally orthogonal peptide-docking interface is embedded into the extracellular domain of the CAR, converting a fixed cellular product into a programmable platform that can be redirected, selectively expanded, or precisely tracked by administering a modular adapter molecule. See related article by Kuo et al., p. XX.
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