决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
英文原题:CAR-NK Cells for Cancer Therapy: Molecular Redesign of the Innate Antineoplastic Response.
CAR-NK Cells for Cancer Therapy: Molecular Redesign of the Innate Antineoplastic Response.
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嵌合抗原受体(CAR)已成为一种强大的合成生物学技术,在T细胞和NK细胞中均展现出多样化的应用能力。尽管CAR-T 细胞在临床试验中取得了成功,但在不良事件和长期疗效方面仍存在若干挑战有待解决。NK细胞作为一种有吸引力的替代方案,在治疗实体瘤和血液肿瘤方面具有优于T细胞的固有优势。早期临床前和临床试验表明,其至少具有两大优势:安全性改善以及由于HLA非依赖性而可作为一种即用型方案应用于患者。由于CAR NK向临床试验的转化尚处于早期阶段,目前可获得的数据有限。通过分析这些结果,CAR NK细胞似乎可以降低癌症患者发生细胞因子释放综合征(CRS)或移植物抗宿主病(GvHD)的概率,从而减少安全性方面的担忧。
此外,NK细胞治疗方法可通过与免疫检查点抑制剂联合使用以及通过引入基因回路来指导携带CAR的细胞行为而得到增强。本综述描述了用于修饰NK细胞的CAR技术,以及在这一免疫治疗新领域中从临床前研究向早期临床试验的转化。
The Chimeric Antigen Receptor (CAR) has arisen as a powerful synthetic biology-based technology with demonstrated versatility for implementation in T and NK cells. Despite CAR T cell successes in clinical trials, several challenges remain to be addressed regarding adverse events and long-term efficacy. NK cells present an attractive alternative with intrinsic advantages over T cells for treating solid and liquid tumors.
Early preclinical and clinical trials suggest at least two major advantages: improved safety and an off-the-shelf application in patients due to its HLA independence. Due to the early stages of CAR NK translation to clinical trials, limited data is currently available. By analyzing these results, it seems that CAR NK cells could offer a reduced probability of Cytokine Release Syndrome (CRS) or Graft versus Host Disease (GvHD) in cancer patients, reducing safety concerns.
Furthermore, NK cell therapy approaches may be boosted by combining it with immunological checkpoint inhibitors and by implementing genetic circuits to direct CAR-bearing cell behavior. This review provides a description of the CAR technology for modifying NK cells and the translation from preclinical studies to early clinical trials in this new field of immunotherapy.
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