Even though chemotherapy and immunotherapy emerged to limit continual and unregulated proliferation of cancer cells, currently available therapeutic agents are associated with high toxicity levels and low success rates. Additionally, ongoing multi-targeted therapies are limited only for few carcinogenesis pathways, due to continually emerging and evolving mutations of proto-oncogenes and tumor-suppressive genes. CRISPR/Cas9, as a specific gene-editing tool, is used to correct causative mutations with minimal toxicity, but is also employed as an adjuvant to immunotherapy to achieve a more robust immunological response. Some of the most critical limitations of the CRISPR/Cas9 technology include off-target mutations, resulting in nonspecific restrictions of DNA upstream of the Protospacer Adjacent Motifs (PAM), ethical agreements, and the lack of a scientific consensus aiming at risk evaluation. Currently, CRISPR/Cas9 is tested on animal models to enhance genome editing specificity and induce a stronger anti-tumor response. Moreover, ongoing clinical trials use the CRISPR/Cas9 system in immune cells to modify genomes in a target-specific manner. Recently, error-free in vitro systems have been engineered to overcome limitations of this gene-editing system. The aim of the article is to present the knowledge concerning the use of CRISPR Cas9 technique in targeting treatment-resistant cancers. Additionally, the use of CRISPR/Cas9 is aided as an emerging supplementation of immunotherapy, currently used in experimental oncology. Demonstrating further, applications and advances of the CRISPR/Cas9 technique are presented in animal models and human clinical trials. Concluding, an overview of the limitations of the gene-editing tool is proffered.

中文翻译：

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CRISPR/Cas9 在癌症免疫治疗中的应用：动物模型和人体临床试验


尽管化疗和免疫疗法的出现是为了限制癌细胞的持续和不受控制的增殖，但目前可用的治疗药物具有高毒性水平和低成功率。此外，由于原癌基因和肿瘤抑制基因不断出现和进化的突变，正在进行的多靶点治疗仅限于少数致癌途径。 CRISPR/Cas9作为一种特定的基因编辑工具，用于以最小的毒性纠正致病突变，但也可用作免疫治疗的佐剂，以实现更强大的免疫反应。 CRISPR/Cas9 技术的一些最关键的限制包括脱靶突变，导致原型间隔子相邻基序 (PAM) 上游 DNA 的非特异性限制、伦理协议以及缺乏针对风险评估的科学共识。目前，CRISPR/Cas9正在动物模型上进行测试，以增强基因组编辑特异性并诱导更强的抗肿瘤反应。此外，正在进行的临床试验在免疫细胞中使用 CRISPR/Cas9 系统以特定目标的方式修改基因组。最近，无差错的体外系统被设计用来克服这种基因编辑系统的局限性。本文的目的是介绍有关使用 CRISPR Cas9 技术靶​​向治疗耐药癌症的知识。此外，CRISPR/Cas9 的使用有助于作为目前用于实验肿瘤学的免疫疗法的新兴补充。进一步展示了 CRISPR/Cas9 技术在动物模型和人体临床试验中的应用和进展。最后，概述了基因编辑工具的局限性。