肿瘤细胞治疗研究
英文原题：Stem cells at the tumor frontier: Mechanistic insights, therapeutic challenges, and emerging horizons.
Stem cells at the tumor frontier: Mechanistic insights, therapeutic challenges, and emerging horizons.
基于干细胞的方法通过结合靶向递送、免疫调节和细胞工程，正在迅速扩展抗癌治疗的手段。
基于干细胞的方法通过结合靶向递送、免疫调节和细胞工程，正在迅速扩展抗癌治疗手段。本综述综合了四个相互关联领域的当前知识：造血干细胞（HSCs），其作为移植物来源抗肿瘤免疫的介导者以及谱系工程化免疫效应细胞的平台；间充质基质/干细胞（MSCs），其表现出肿瘤趋向性归巢，并可在肿瘤微环境（TME）中作为情境依赖性调节因子或载体发挥作用；诱导多能干细胞（iPSCs），其提供了生成自体或异体免疫效应细胞及设计者细胞疗法的可扩展来源；以及癌症干细胞（CSCs），其是治疗耐药、微小残留病和复发的根源。我们评估了有前景的转化策略，包括嵌合抗原受体（CAR）工程化的HSC和iPSC衍生效应细胞、MSC介导的治疗药物靶向递送，以及细胞外囊泡（EVs）工程化，同时探讨了关键的生物学和制造障碍。主要挑战包括MSCs情境依赖性的促肿瘤与抗肿瘤活性、多能干细胞衍生制品相关的致瘤风险、免疫兼容性和应答持久性，以及产品异质性给可重复性和监管评估带来的困难。为加速安全的临床转化，我们建议标准化功能表征检测、在多种肿瘤模型中进行严格的体内安全性和有效性测试、采用稳健的效价和身份指标，以及将分子工程与可控安全开关和免疫调节辅助手段进行策略性组合。通过将机制性见解与转化优先事项相结合，该领域可以优先选择最有可能实现持久、安全且广泛适用的基于细胞的癌症疗法的方法。
Stem cell-based approaches are rapidly expanding the therapeutic repertoire against cancer by combining targeted delivery, immune modulation, and cellular engineering. This review synthesizes current knowledge across four interconnected domains: hematopoietic stem cells (HSCs), which serve as mediators of graft-derived antitumor immunity and as platforms for lineage-engineered immune effectors; mesenchymal stromal/stem cells (MSCs), which exhibit tumor-tropic homing and can function as context-dependent modulators or carriers within the tumor microenvironment (TME); induced pluripotent stem cells (iPSCs), which provide a scalable source for generating autologous or allogeneic immune effector cells and designer cell therapies; and cancer stem cells (CSCs), which underlie therapeutic resistance, minimal residual disease, and relapse. We evaluate promising translational strategies including chimeric antigen receptors (CAR)-engineered HSC and iPSC-derived effectors, MSC-mediated targeted delivery of therapeutics, and extracellular vesicles (EVs) engineering alongside critical biological and manufacturing barriers. Principal challenges include the context-dependent pro- versus antitumor activities of MSCs, the tumorigenic risk associated with pluripotent-derived products, immunological compatibility and durability of responses, and product heterogeneity that complicates reproducibility and regulatory assessment. To accelerate safe clinical translation, we recommend standardized functional characterization assays, rigorous in vivo safety and efficacy testing across tumor models, adoption of robust potency and identity metrics, and strategic combinations of molecular engineering with controllable safety switches and immune-modulating adjuncts. By aligning mechanistic insight with translational priorities, the field can prioritize approaches most likely to deliver durable, safe, and broadly applicable cell-based cancer therapies.
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