CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Nano-optogenetic immunotherapy.
Nano-optogenetic immunotherapy.
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过去5年,基于嵌合抗原受体(CAR)T细胞的免疫疗法日益用于癌症临床治疗。CAR-T 治疗利用基因修饰T细胞,使其在细胞表面表达合成CAR分子。截至目前,美国食品药品监督管理局已批准多达6种CAR-T 细胞产品,用于治疗白血病、淋巴瘤和多发性骨髓瘤;另有数百种CAR-T 产品正在实体瘤临床试验中。在基础研究和临床应用中,CAR-T 免疫治疗均已取得令人振奋的进展,带来显著缓解或抑制癌症的效果。
然而,CAR-T 免疫治疗仍有重要安全问题,例如抗原特异性不足所致的“靶向肿瘤、同时误伤肿瘤外正常组织”细胞毒性。此外,输注的CAR-T 细胞若发生不受控的大规模活化,可能引起严重全身炎症,导致细胞因子释放综合征和神经毒性。为应对这些挑战,需要将纳米技术、光遗传学与免疫工程相结合,开发可在时间和空间上精确控制的CAR-T 细胞,使治疗性免疫细胞能够通过无线光信号调节活性,从而在肿瘤微环境中实现个体化治疗。
Chimeric antigen receptor (CAR) T cell-based immunotherapy has been increasingly used in the clinic for cancer intervention over the past 5 years. CAR T-cell therapy takes advantage of genetically-modified T cells to express synthetic CAR molecules on the cell surface. To date, up to six CAR T cell therapy products have been approved by the Food and Drug Administration for the treatment of leukaemia, lymphoma, and multiple myeloma.
In addition, hundreds of CAR-T products are currently under clinical trials to treat solid tumours. In both the fundamental research and clinical applications, CAR T cell immunotherapy has achieved exciting progress with remarkable remission or suppression of cancers.
However, CAR T cell-based immunotherapy still faces significant safety issues, as exemplified by "on-target off-tumour" cytotoxicity due to lack of strict antigen specificity.
In addition, uncontrolled massive activation of infused CAR T cells may create severe systemic inflammation with cytokine release syndrome and neurotoxicity. These challenges call for a need to combine nanotechnology and optogenetics with immunoengineering to develop spatiotemporally-controllable CAR T cells, which enable wireless photo-tunable activation of therapeutic immune cells to deliver personalised therapy in the tumour microenvironment.
在 PubMed 查看 → 出版商原文(DOI) 全文 PDF(PMC)· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →
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