CRISPR/Cas9 技术促进癌症免疫治疗的进步:从揭示调控机制到治疗应用。
CRISPR/Cas9 technology for advancements in cancer immunotherapy: from uncovering regulatory mechanisms to therapeutic applications.
发表日期:2024 Oct 19
作者:
Xiaohang Feng, Zhengxing Li, Yuping Liu, Di Chen, Zhuolong Zhou
来源:
Cellular & Molecular Immunology
摘要:
近年来,免疫治疗作为肿瘤治疗的新领域发展迅速。然而,由于肿瘤细胞的免疫逃避机制、诱导免疫抑制肿瘤微环境(TME)、减少抗原递送等,肿瘤免疫治疗的疗效并不理想。CRISPR/Cas9基因编辑技术可以精确修饰免疫和肿瘤细胞通过针对免疫检查点分子和免疫调节基因来提高免疫治疗的疗效,从而得到了巨大的发展和应用。目前的临床试验中,CRISPR/Cas9在肿瘤免疫治疗中的应用还存在许多障碍,如确保基因编辑的准确性和安全性、克服过度反应的免疫反应、解决体内药物递送的挑战等。在此我们对CRISPR/Cas9在肿瘤治疗中的应用进行系统综述,以解决上述存在的问题。我们专注于免疫调节基因的CRISPR/Cas9筛选和鉴定、免疫检查点分子的靶向、免疫调节剂的操作、增强肿瘤特异性抗原呈递和调节免疫细胞功能。其次,我们还重点介绍了CRISPR/Cas9在动物模型和各种递送系统中的临床前研究,评估了CRISPR/Cas9技术在肿瘤免疫治疗中的有效性和安全性。最后,提出了将 CRISPR/Cas9 敲低与其他免疫疗法相结合的潜在协同方法。这项研究强调了 CRISPR/Cas9 重塑肿瘤免疫治疗格局的变革潜力,并为癌症患者的新治疗策略提供了见解。© 2024。作者。
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.© 2024. The Author(s).