基因编辑增强癌症细胞疗法的疗效。
Gene editing to enhance the efficacy of cancer cell therapies.
机构信息
Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA; Program in Biophysics, Stanford University, Stanford, CA, USA; Medical Scientist Training Program, Stanford University, Stanford, CA, USA.
Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA; Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
出版信息
Mol Ther. 2021 Nov 3;29(11):3153-3162. doi: 10.1016/j.ymthe.2021.10.001. Epub 2021 Oct 18.
Adoptive T cell therapies have shown impressive signals of activity, but their clinical impact could be enhanced by technologies to increase T cell potency and diminish the cost and labor involved in manufacturing these products. Gene editing platforms are under study in this arena to (1) enhance immune cell potency by knocking out molecules that inhibit immune responses; (2) deliver genetic payloads into precise genomic locations and thereby enhance safety and/or improve the gene expression profile by leveraging physiologic promoters, enhancers, and repressors; and (3) enable off-the-shelf therapies by preventing alloreactivity and immune rejection. This review discusses gene editing approaches that have been the best studied in the context of human T cells and adoptive T cell therapies, summarizing their current status and near-term potential for translation.
过继性 T 细胞疗法已显示出显著的疗效，但通过提高 T 细胞效力的技术并降低制造这些产品的成本和劳动力，其临床效果可能会得到增强。基因编辑平台正在该领域进行研究，以（1）通过敲除抑制免疫反应的分子来增强免疫细胞的效力；（2）将遗传有效载荷递送至精确的基因组位置，从而通过利用生理启动子、增强子和阻遏子来提高安全性和/或改善基因表达谱；（3）通过防止同种异体反应和免疫排斥来实现现成的治疗方法。本文综述了在人类 T 细胞和过继性 T 细胞疗法背景下研究得最多的基因编辑方法，总结了它们目前的状况和近期转化的潜力。
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