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CRISPR/Cas9 技术在癌症免疫治疗中的进展:从调控机制发现到治疗应用

英文原题:CRISPR/Cas9 technology for advancements in cancer immunotherapy: from uncovering regulatory mechanisms to therapeutic applications.

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CRISPR/Cas9 technology for advancements in cancer immunotherapy: from uncovering regulatory mechanisms to therapeutic applications.

PubMed 2024/10/19(内容时间) Exp Hematol Oncol Q1 · IF 17.5(JCR 2025)

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中文摘要

近年来,免疫治疗作为肿瘤治疗新领域发展迅速。然而,由于肿瘤细胞免疫逃逸、诱导免疫抑制性肿瘤微环境(TME)和抗原递送减少等因素,肿瘤免疫治疗疗效仍不理想。CRISPR/Cas9 基因编辑技术可精准改造肿瘤中的免疫细胞和肿瘤细胞,并通过靶向免疫检查点分子和免疫调节基因提高免疫治疗疗效,因而得到广泛发展和应用。目前临床试验中,CRISPR/Cas9 用于肿瘤免疫治疗仍面临许多障碍,例如确保基因编辑的准确性和安全性、克服过度免疫应答以及解决体内药物递送挑战。本文系统综述 CRISPR/Cas9 在肿瘤治疗中的应用,以应对上述问题。

我们重点讨论利用 CRISPR/Cas9 筛选和鉴定免疫调节基因、靶向免疫检查点分子、调控免疫调节因子、增强肿瘤特异性抗原呈递以及调节免疫细胞功能。

此外,我们还介绍 CRISPR/Cas9 在动物模型中的临床前研究和各类递送系统,并评估 CRISPR/Cas9 技术用于肿瘤免疫治疗的疗效与安全性。

最后,提出将 CRISPR/Cas9 基因敲低与其他免疫疗法联合的潜在协同策略。本研究凸显 CRISPR/Cas9 重塑肿瘤免疫治疗格局的变革性潜力,并为癌症患者的新型治疗策略提供见解。

展开英文摘要原文

In recent years, immunotherapy has developed rapidly as a new field of tumour therapy.

However, the efficacy of tumour immunotherapy is not satisfactory due to the immune evasion mechanism of tumour cells, induction of immunosuppressive tumour microenvironment (TME), and reduction of antigen delivery, etc. CRISPR/Cas9 gene editing technology can accurately modify immune and tumour cells in tumours, and improve the efficacy of immunotherapy by targeting immune checkpoint molecules and immune regulatory genes, which has led to the great development and application.

In current clinical trials, there are still many obstacles to the application of CRISPR/Cas9 in tumour immunotherapy, such as ensuring the accuracy and safety of gene editing, overcoming overreactive immune responses, and solving the challenges of in vivo drug delivery.

Here we provide a systematic review on the application of CRISPR/Cas9 in tumour therapy to address the above existing problems.

We focus on CRISPR/Cas9 screening and identification of immunomodulatory genes, targeting of immune checkpoint molecules, manipulation of immunomodulators, enhancement of tumour-specific antigen presentation and modulation of immune cell function. Second, we also highlight preclinical studies of CRISPR/Cas9 in animal models and various delivery systems, and evaluate the efficacy and safety of CRISPR/Cas9 technology in tumour immunotherapy.

Finally, potential synergistic approaches for combining CRISPR/Cas9 knockdown with other immunotherapies are presented.

This study underscores the transformative potential of CRISPR/Cas9 to reshape the landscape of tumour immunotherapy and provide insights into novel therapeutic strategies for cancer patients.

论文信息

作者
Feng X、Li Z、Liu Y、Chen D、Zhou Z
第一作者单位
Department of Colorectal Surgery, the Second Affiliated Hospital, and Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.United Kingdom
通讯作者单位
Department of Colorectal Surgery, the Second Affiliated Hospital, and Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China. zhuolongzhou@intl.zju.edu.cn.United Kingdom
文献类型
综述
期刊
Experimental hematology & oncology2024 Oct 19
原文标识
PubMed 39427211 · DOI 10.1186/s40164-024-00570-y