Department of Hepatobiliary and Pancreas Surgery, the Second Hospital of Jilin University, Changchun 130041, China.
Department of Hepatobiliary and Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun 130021, China.
Hepatobiliary Pancreat Dis Int. 2018 Aug;17(4):301-309. doi: 10.1016/j.hbpd.2018.05.005. Epub 2018 May 24.
BACKGROUND: Chimeric antigen receptor-engineered T-cell (CAR-T) therapy is a newly developed immunotherapy used in the treatment of cancers. Because CAR-T therapy has shown great success in treating CD19-positive hematological malignancies, its application has been explored in the treatment of solid tumors, such as liver cancer. In this review, we discuss the immune characteristics of liver cancer, the obstacles encountered during the application of CAR-T therapy, and preclinical and clinical progress in the use of CAR-T therapy in patients with liver cancer. DATA SOURCES: The data on CAR-T therapy related to liver cancers were collected by searching PubMed and the Web of Science databases prior to December 2017 with the keywords "chimeric antigen receptor", "CAR-T", "liver cancer", "hepatocellular carcinoma", and "solid tumor". Additional articles were identified by manual search of references found in the primary articles. The data for clinical trials were collected by searching ClinicalTrials.gov. RESULTS: The liver has a tolerogenic nature in the intrahepatic milieu and its tumor microenvironment significantly affects tumor progression. The obstacles that reduce the efficacy of CAR-T therapy in solid tumors include a lack of specific tumor antigens, limited trafficking and penetration of CAR-T cells to tumor sites, and an immunosuppressive tumor microenvironment. To overcome these obstacles, several strategies have emerged. In addition, several strategies have been developed to manage the side effects of CAR-T, including enhancing the selectivity of CARs and controlling CAR-T activity. To date, no clinical trials of CAR-T therapy against HCC have been completed. However, preclinical studies in vitro and in vivo have shown potent antitumor efficacy. Glypican-3, mucin-1, epithelial cell adhesion molecule, carcinoembryonic antigen, and other targets are currently being studied. CONCLUSIONS: The application of CAR-T therapy for liver cancer is just beginning to be explored and more research is needed. However, we are optimistic that CAR-T therapy will offer a new approach for the treatment of liver cancers in the future.
背景：嵌合抗原受体修饰的 T 细胞（CAR-T）疗法是一种新开发的免疫疗法，用于治疗癌症。由于 CAR-T 疗法在治疗 CD19 阳性血液恶性肿瘤方面取得了巨大成功，因此其在治疗肝癌等实体瘤中的应用也得到了探索。在本综述中，我们讨论了肝癌的免疫特征、CAR-T 疗法应用中遇到的障碍，以及 CAR-T 疗法在肝癌患者中的临床前和临床进展。
数据来源：通过在 PubMed 和 Web of Science 数据库中搜索关键词“嵌合抗原受体”、“CAR-T”、“肝癌”、“肝细胞癌”和“实体瘤”，检索截至 2017 年 12 月与肝癌相关的 CAR-T 疗法数据。通过对主要文章中发现的参考文献进行手动搜索，确定了其他文章。通过在 ClinicalTrials.gov 上搜索，获取临床试验数据。
结果：肝脏在肝内环境中具有免疫耐受特性，其肿瘤微环境显著影响肿瘤进展。在实体瘤中降低 CAR-T 疗法疗效的障碍包括缺乏特异性肿瘤抗原、CAR-T 细胞向肿瘤部位的转移和渗透有限以及免疫抑制性肿瘤微环境。为了克服这些障碍，已经出现了几种策略。此外，还开发了几种策略来管理 CAR-T 的副作用，包括增强 CAR 的选择性和控制 CAR-T 活性。迄今为止，尚无针对 HCC 的 CAR-T 疗法的临床试验完成。然而，体外和体内的临床前研究表明其具有强大的抗肿瘤疗效。目前正在研究磷脂酰聚糖-3、黏蛋白-1、上皮细胞黏附分子、癌胚抗原等靶点。
结论：CAR-T 疗法在肝癌中的应用才刚刚开始探索，还需要更多的研究。但是，我们乐观地认为，CAR-T 疗法将为未来肝癌的治疗提供新的方法。
Hepatobiliary Pancreat Dis Int. 2018-5-24
Sci China Life Sci. 2018-11-7
J Immunother Cancer. 2021-4
Mamm Genome. 2018-7-9
Mol Cancer. 2018-1-12
Int J Nanomedicine. 2025-6-13
Ecancermedicalscience. 2024-11-8
Hum Vaccin Immunother. 2024-12-31
Braz J Med Biol Res. 2024
Med Oncol. 2024-10-14
J Cancer Res Clin Oncol. 2024-6-24
Zotero 插件