Purpose of Review

T cell-based cellular and antibody immunotherapies have dramatically altered the landscape of cancer treatment over the past decade. Over the same time span, gene editing technologies have enabled unprecedented degrees of genetic control.

Recent Findings

Knock-outs of endogenous genes, especially based on electroporation of targetable nucleases such as CRISPR/Cas9, have rapidly proliferated. Simultaneous introduction of large DNA sequences can integrate new synthetic genetic instructions with specific endogenous loci to alter T cell function and specificity. Recently developed discovery technologies to perform genome-wide knock-out and large-scale knock-in screens in T cells can rapidly identify endogenous gene targets and therapeutic knock-in programs.

Summary

Endogenous gene knock-outs and targeted knock-ins may offer the chance to expand beyond the current limitations of randomly integrating viral vector-based T cell therapies, and extend immunotherapies’ therapeutic advances to wider hematologic and solid tumor indications.

中文翻译：

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细胞免疫疗法中内源基因的编辑。

审查目的

过去十年，基于 T 细胞的细胞和抗体免疫疗法极大地改变了癌症治疗的格局。与此同时，基因编辑技术使基因控制达到了前所未有的程度。

最近的发现

内源基因的敲除，特别是基于 CRISPR/Cas9 等靶向核酸酶的电穿孔，已经迅速普及。同时引入大的 DNA 序列可以将新的合成遗传指令与特定的内源基因座整合，以改变 T 细胞的功能和特异性。最近开发的在 T 细胞中进行全基因组敲除和大规模敲入筛选的发现技术可以快速识别内源基因靶标和治疗性敲入程序。

概括

内源基因敲除和靶向敲入可能会提供突破目前随机整合基于病毒载体的 T 细胞疗法的局限性的机会，并将免疫疗法的治疗进展扩展到更广泛的血液学和实体瘤适应症。