PD-1/PD-L1单抗药物抗肿瘤免疫治疗相关不良反应及超进展疾病研究进展OACSTPCD
Advances in treatment of immune-related adverse reactions and hyperprogressive diseases associated with antitumor immunotherapy with PD-1/PD-L1 monoclonal antibody drugs
近年来,免疫治疗药物的开发和临床应用取得了突破性进展,其中程序性死亡受体1(PD-1)及其配体(PD-L1)作为第二代免疫检查点抑制剂的临床靶点,已成为新药研发的热点之一.目前,美国食品药品监督管理局和我国国家食品药品监督管理总局已批准多种PD-1/PD-L1单克隆抗体(单抗)药物如纳武利尤单抗、帕博利珠单抗和阿替利珠单抗等上市,用于治疗小细胞肺癌、直肠癌、结肠癌和黑色素瘤等.然而在临床应用中发现,PD-1/PD-L1单抗药物在肺、肝、肾、胃肠道系统、内分泌系统和皮肤等均可引起患者发生不同程度的免疫相关不良反应,甚至出现超进展疾病(hyperprogressive disease)情况.加强对PD-1/PD-L1单抗药物的临床应用进行有效的监测与管理,对症使用相关药物,可改善免疫治疗进程,减少免疫治疗对患者产生的不良反应及超进展疾病的影响.
There have been breakthroughs in the development and clinical application of immuno-therapeutic agents in recent years.As the clinical targets of second-generation immune checkpoint inhibitors(ICIs),programmed death-1(PD-1)and its ligand(programmed death-ligand 1,PD-L1)have become one of the hot spots in drug discovery.The Food and Drug Administration of the USA and National Medical Products Administration in China have approved a variety of PD-1/PD-L1 monoclonal antibody drugs(such as nivolumab,pembrolizumab and atezolizumab),which are marketed for the treatment of small-cell lung cancer,rectal cancer,colon cancer,and melanoma,among other diseases.However,in the clinical application of PD-1/PD-L1 monoclonal antibody drugs,it is found that they can cause different degrees of immune-related adverse reactions in the lung,liver,kidney,gastrointestinal system,endocrine system and skin,and even the emergence of hyperprogressive disease.Effective monitoring and management of clinical applications of PD-1/PD-L1 monoclonal antibody drugs and rational use of some drugs can improve the immunotherapy process and reduce the effects of adverse reactions and hyperprogressive diseases in patients under immunotherapy.
王鹏焱;林子又;朱凯;张小雷
长春中医药大学药学院,吉林长春 130117中山大学药学院,广东 广州 510006
药学
免疫治疗程序性死亡受体1程序性死亡受体配体1免疫相关不良反应超进展疾病
immunotherapyprogrammed death-1programmed death-ligand 1immune related adverse reactionshyperprogression disease
《中国药理学与毒理学杂志》 2024 (001)
56-69 / 14
国家自然科学基金(82273958);吉林省科技发展计划(20230204063YY);吉林省科技发展计划(20210204055YY) National Natural Science Foundation of China(82273958);Jilin Province Science and Technology Development Project(20230204063YY);and Jilin Province Science and Technology Development Project(20210204055YY)
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