IL-2修饰药物分子研发进展  

Advances of modified IL-2 molecules in drug development

作　　者：黄丽晶 马小涵 李晨辉 王红权 HUANG Lijing;MA Xiaohan;LI Chenhui;WANG Hongquan(Hebei Key Laboratory of Autoimmunity Disease Drug Research,Hebei Fitness Biotechnology Co.,Ltd.,Shijiazhuang 050035,Hebei,China;Shijiazhuang Technology Innovation Centre of Autoimmune Disease Drug,Hebei Fitness Biotechnology Co.,Ltd.,Shijiazhuang 050035,Hebei,China)

机构地区：[1]河北菲尼斯生物技术有限公司河北省自身免疫药物研究重点实验室,河北石家庄050035 [2]河北菲尼斯生物技术有限公司石家庄自身免疫药物技术创新中心,河北石家庄050035

出　　处：《生物工程学报》2022年第9期3279-3290,共12页Chinese Journal of Biotechnology

基　　金：河北省省级科技计划(20372406D)。

摘　　要：白细胞介素2(interleukin-2,IL-2)是免疫系统的关键调控因子,其在免疫刺激和免疫抑制过程中均发挥重要作用。作为第一个上市的肿瘤免疫疗法药物,IL-2因疗效不足及严重不良反应导致其临床应用受到很大限制。通过对IL-2进行修饰,可延长药物半衰期,提高细胞特异性,使之更加特异地作用于效应T细胞或调节性T细胞,用于肿瘤或自身免疫病的治疗,是目前免疫治疗领域的研发热点之一。其中聚乙二醇(polyethylene glycol,PEG)修饰IL-2分子与PD-1单抗联用,在黑色素瘤治疗上显现出很好的潜力;同时,还有更多用于肿瘤和自身免疫病治疗的IL-2修饰分子也已进入临床研究阶段。相信将有IL-2修饰分子获得监管部门批准,成为人类对抗免疫相关疾病的有力武器。Interleukin-2(IL-2)is one of the most important regulators in immune system,as it plays an essential part both in immune activation and suppression.However,as the first immunotherapy drug approved for the treatment of cancer,IL-2 is limited in clinical application by the serious adverse reactions.The long-felt needs in clinical practice,including prolonged half-lives,T cell subset specificity,and toxicity reduction can be achieved by polyethylene glycol(PEG)modification,Fc fusing,or protein mutation of IL-2.NKTR-214,the most advanced IL-2 pathway─targeted agent in clinical development for oncology,shows exciting results in treatment of melanoma in combination with nivolumab.At the same time,many more other modified molecules against cancer and autoimmune diseases are being tested in clinical research,an exciting future lying ahead for IL-2 therapeutics.

关 键 词：免疫治疗 蛋白修饰 肿瘤 自身免疫病 白细胞介素2 程序性细胞死亡蛋白1 PEG修饰 T细胞调节 

分 类 号：R914[医药卫生—药物化学]