嵌合抗原受体细胞疗法在肝癌治疗中的前景与挑战  

Prospects and challenges of chimeric antigen receptor cell therapy in hepatocellular carcinoma

作　　者：卫强 唐琳 潘晟 徐骁 Wei Qiang;Tang Lin;Pan Sheng;Xu Xiao(Department of Hepatobiliary&Pancreatic Surgery and Minimally Invasive Surgery,Affiliated People′s Hospital of Hangzhou Medical College(Zhejiang Provincial People′s Hospital),Hangzhou 310014,China;Zhejiang University School of Medicine,Hangzhou 310058,China)

机构地区：[1]杭州医学院附属人民医院(浙江省人民医院)肝胆胰外科、微创外科,杭州310014 [2]浙江大学医学院,杭州310058

出　　处：《中华消化外科杂志》2025年第2期178-183,共6页Chinese Journal of Digestive Surgery

基　　金：国家自然科学基金(92159202);国家重点研发计划(2021YFA1100500);浙江省重点研发计划(2021C03118)。

摘　　要：嵌合抗原受体(CAR)细胞疗法为肝癌治疗提供了新希望,但仍面临多个挑战。首先,肝癌高度异质性导致缺乏理想靶点,使得CAR细胞难以精准识别并有效杀伤肿瘤细胞。其次,肝癌的免疫抑制微环境,如调节性T细胞和髓系抑制细胞,会削弱CAR细胞的功能,进一步影响治疗效果。此外,CAR细胞疗法的安全性问题,如细胞因子释放综合征和神经毒性,也制约其临床应用。最后,CAR细胞疗法的高成本和复杂的生产流程是其普及应用的主要障碍。未来研究应聚焦于优化靶点选择,特别是针对肝癌特异性分子标记的靶点;增强CAR细胞在免疫抑制环境中的耐受性;提高治疗安全性,并简化生产工艺以降低成本。解决这些关键瓶颈将促进CAR细胞疗法在肝癌等实体肿瘤中的广泛应用,推动肝癌治疗的革新。笔者查阅相关文献并结合临床实践,探讨CAR细胞疗法治疗肝癌的前景和挑战,旨在为其临床应用提供新思路。Chimeric antigen receptor(CAR)cell therapy offers promising new avenues for the treatment of hepatocellular carcinoma.However,several challenges hinder its full potential.Firstly,the high heterogeneity of hepatocellular carcinoma results in a lack of ideal targets,complicating the ability of CAR cells to specifically recognize and effectively eliminate tumor cells.Secondly,the immunosuppressive microenvironment of hepatocellular carcinoma,characterized by regulatory T cells and myeloid‐derived suppressor cells,diminishes the efficacy of CAR cell therapy,further affecting treatment efficacy.Additionally,safety concerns such as cytokine release syndrome and neurotoxicity remain significant obstacles to clinical application.Finally,the high cost and complex manufacturing processes involved in CAR cell therapy present major barriers to its widespread use.Future research should focus on optimizing target selection,particularly by identifying hepatocellular carcinoma specific molecular markers;improving CAR cells resilience in immunosuppressive environments;enhancing safety protocols;and streamlining production methods to reduce costs.Addressing these critical issues will facilitate the broader application of CAR cell therapy in hepatocellular carcinoma and other solid tumors,paving the way for a paradigm shift in cancer treatment.Based on relevant literature and combined it with clinical practice,the authors explore the prospects and challenges of CAR cell therapy for the treatment of hepatocellular carcinoma,aiming to provide new ideas for its clinical application.

关 键 词：肝肿瘤 细胞治疗 嵌合抗原受体细胞疗法 治疗 疗效 

分 类 号：R73[医药卫生—肿瘤]