GenLab Biosolutions Private Limited, Bangalore, Karnataka, 560043, India.
Mol Biol Rep. 2022 Jul;49(7):7069-7077. doi: 10.1007/s11033-022-07147-0. Epub 2022 Feb 5.
Novel cellular immunotherapy with engineered T cells has improved cancer treatment and established therapeutic promises to prevent tumor formation in clinical studies. Due to certain restrictions and difficulties, CAR and TCR T-cells therapies were inadequate at points. CRISPR Cas9 genome-editing tool has significant potential for these two cell-based therapies. As a specialized gene-editing technique, CRISPR Cas9 is used to repair genetic alternations with minimal damage. It is used as an adjunct to immunotherapy to stimulate a more robust immune response. CRISPR has long outpaced other target-specific genome editing methods such as ZFNs and TALEN because of its high efficiency, competence in targeting, and stable operating conditions. CRISPR can overcome the two major drawbacks of universal CAR T cells: allorejection and graft-vs-host disease. TCR-based T cell treatment can reduce inappropriate binding between endogenous and transgenic TCR, resulting in a reduction of severe toxicity. The CAR and TCR T based cell therapies uphold an excellent future for tumor malignancies. This article has elucidated the administration of CRISPR Cas9 in novel cellular immunotherapy, CAR, and TCR T cell therapy. However, this article did not fail to observe this technology's ethical concerns, limitations, and challenges. Furthermore, the article compares CRISPR-mediated allogeneic CAR T cell to TCR-T cell therapy.
新型细胞免疫疗法中的工程化 T 细胞改善了癌症治疗,并在临床研究中为预防肿瘤形成确立了治疗承诺。由于某些限制和困难,CAR 和 TCR T 细胞疗法在某些方面存在不足。CRISPR Cas9 基因组编辑工具对这两种基于细胞的疗法具有重大潜力。作为一种专门的基因编辑技术,CRISPR Cas9 可用于最小化损伤修复遗传改变。它被用作免疫疗法的辅助手段,以刺激更强大的免疫反应。由于其高效率、靶向能力和稳定的操作条件,CRISPR 长期以来一直超过其他靶向特定基因组编辑方法,如 ZFNs 和 TALEN。CRISPR 可以克服通用 CAR T 细胞的两个主要缺点:同种异体排斥和移植物抗宿主病。基于 TCR 的 T 细胞治疗可以减少内源性和转基因 TCR 之间的不当结合,从而降低严重毒性。CAR 和 TCR T 细胞为肿瘤恶性肿瘤提供了良好的未来。本文阐述了 CRISPR Cas9 在新型细胞免疫疗法、CAR 和 TCR T 细胞治疗中的应用。然而,本文并没有忽视这项技术的伦理问题、局限性和挑战。此外,本文还比较了 CRISPR 介导的同种异体 CAR T 细胞与 TCR-T 细胞治疗。
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