CAR-T细胞治疗产品非临床药效学研究关注点  

Considerations of Non-clinical Pharmacodynamic Study of CAR-T Cell Therapy Products

作　　者：侯田田 黄瑛[1] 霍艳[1] Hou Tiantian;Huang Ying;Huo Yah(Beijing Key Laboratory,National Center for Safety Evaluation of Drugs,National Institutes for Food and Drug Control,Beijing 100176,China)

机构地区：[1]中国食品药品检定研究院药物非临床安全评价研究北京市重点实验室,北京100176

出　　处：《中国药事》2018年第9期1232-1238,共7页Chinese Pharmaceutical Affairs

基　　金：十二五国家科技重大专项"生物大分子药物特殊评价关键技术研究"(编号2015ZX09501007-004);中国食品药品检定研究院学科带头人培养基金(编号2015X1)

摘　　要：CAR-T细胞(Chimeric Antigen Receptor T Cells,CAR-T)是一种表达嵌合抗原受体的基因工程T细胞,也称"活的药物",可以增强基因工程T细胞的特异性,能够以MHC(主要组织相容性复合体,Major Histocompatibility Complex,MHC)非依赖性的方式高度靶向肿瘤抗原,是治疗肿瘤的一种新手段。最近,临床上使用CAR-T细胞治疗复发、难治性血液恶性肿瘤和多发性骨髓瘤取得了很好的疗效;同时,采用CAR-T细胞治疗实体瘤的研发也在积极开展。根据所构建的CAR-T细胞不同的适应证和作用原理,构建不同的动物肿瘤模型,研究CAR-T细胞在动物模型的抗肿瘤活性,可以对CAR-T细胞进行概念验证性研究并证明其体内药效学活性,为临床研究提供有力的数据支持。Chimeric antigen receptor T（CAR-T） cells are genetically engineered T cells that express chimeric antigen receptors, also known as ＂living drugs＂. CAR-T cells can enhance the specificity of genetically engineered T cell, highly target tumor antigens in a major histocompatibility complex（MHC）-independent manner and provide a new approach to the treatment of tumors. Recently, clinical use of CAR-T cells for the treatment of relapsed, refractory hematological malignancies and multiple myeloma has achieved good results; at the same time, CAR-T cells can also be used to treat solid tumors. According to the different indications and mechanism of action of CAR-T cells, different animal tumor models were constructed to study the anti-tumor activities of CAR-T cells in animal models. Proof-of-concept studies could be carried out and in vivo pharmacodynamic activity could be confirmed so as to provide supportive data for clinical study of CAR-T cells.

关 键 词：CAR-T细胞 药效学研究 抗肿瘤活性 毒性 

分 类 号：R96[医药卫生—药理学]