CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Immunotargeting of Cancer Stem Cells.
Immunotargeting of Cancer Stem Cells.
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普遍认为,癌症干细胞(CSC)劫持正常干细胞相关信号通路,以调控自我更新和分化过程。因此,尽管选择性靶向CSC具有重要临床意义,开发此类策略仍面临重大挑战,因为CSC与正常干细胞共享许多维持其生存的关键信号机制。此外,肿瘤异质性和CSC可塑性也会削弱治疗疗效。虽然研究者已大量尝试通过化学抑制Notch、Hedgehog(Hh)和Wnt/β-连环蛋白等发育通路靶向CSC群体,但针对CSC特异性抗原(包括细胞表面靶点)刺激免疫应答的研究相对较少。癌症免疫疗法通过特异性激活免疫细胞并将其重定向至肿瘤细胞,诱发抗肿瘤免疫应答。本综述聚焦靶向CSC的免疫治疗策略,如双特异性抗体和抗体药物候选物、靶向CSC的细胞免疫疗法及免疫疫苗。我们讨论提高不同免疫疗法安全性和疗效的策略,并介绍相关临床开发的现状。
The generally accepted view is that CSCs hijack the signaling pathways attributed to normal stem cells that regulate the self-renewal and differentiation processes.
Therefore, the development of selective targeting strategies for CSC, although clinically meaningful, is associated with significant challenges because CSC and normal stem cells share many important signaling mechanisms for their maintenance and survival.
Furthermore, the efficacy of this therapy is opposed by tumor heterogeneity and CSC plasticity. While there have been considerable efforts to target CSC populations by the chemical inhibition of the developmental pathways such as Notch, Hedgehog (Hh), and Wnt/ -catenin, noticeably fewer attempts were focused on the stimulation of the immune response by CSC-specific antigens, including cell-surface targets.
Cancer immunotherapies are based on triggering the anti-tumor immune response by specific activation and targeted redirecting of immune cells toward tumor cells. This review is focused on CSC-directed immunotherapeutic approaches such as bispecific antibodies and antibody-drug candidates, CSC-targeted cellular immunotherapies, and immune-based vaccines.
We discuss the strategies to improve the safety and efficacy of the different immunotherapeutic approaches and describe the current state of their clinical development.
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