肿瘤的免疫基因治疗——突破与挑战

Immunogene Therapy of Tumors——Breakthrough and Challenge

免疫检查点疗法和嵌合抗原受体T细胞免疫疗法(CAR-T)的发展极大推动了肿瘤免疫治疗在基础和临床研究中的应用。免疫系统清除肿瘤主要包括7个关键步骤:释放抗原、抗原呈递、激活T细胞、T细胞转运、T细胞浸润和存活、识别和消除肿瘤细胞。随着对肿瘤微环境的深入理解和基因编辑工具的快速发展,基因免疫疗法在肿瘤治疗中发挥着重要作用。基因突变的肿瘤细胞通过表面分子变化逃避机体免疫应答,这些突变的基因可以作为治疗的靶标。本文主要介绍免疫系统的抗肿瘤机制和肿瘤的免疫逃逸机制,以及一些最新的基于基因的免疫疗法策略,包括淋巴细胞疗法、免疫检查点疗法、细胞因子疗法和长链非编码RNA疗法等,旨在为肿瘤的免疫基因治疗提供参考。

Therapy approaches of immune checkpoint blockade and chimeric antibody receptor engineered T cell(CAR-T) have elicited remarkable clinical responses in cancer patients. The antitumor immunity process can broadly be divided into seven key steps: antigen release, antigen presentation, T-cell priming, trafficking of T cells, infiltration and survival of T cells, recognizing and killing of cancer cells. With the deepening understanding of tumor microenvironment and the rapid development of gene-editing tools, gene-based immunotherapy is playing a crucial role in cancer treatment.Tumor mainly evades immune response by molecule change. For example, gene loss of phosphate and tension homology deleted on chromsome ten(PTEN) and phosphoinositide 3-kinase(PI3K) pathway activation occur in multiple tumor types, which may be the potential target of the gene therapy. In order to provide a reference for cancer immunotherapy,this review mainly focuses on antitumor mechanism of the immune system, tumor evasion from the host immune response, and some of the most recent and promising gene-based strategies for immunotherapy, which are based on lymphocytes, immune checkpoint blockade, cytokines, and long non-coding RNAs. Besides, approved drug products for immunotherapy have been sorted out for better guidance in cancer treatment.