摘要
近年来,肿瘤免疫调控机制逐渐清晰,随着嵌合抗原受体T细胞免疫疗法获美国FDA批准上市,揭开了肿瘤免疫治疗的新篇章。在肿瘤免疫治疗药物临床前评价过程中,传统的免疫缺陷动物模型存在较多的限制和缺陷,无法模拟人体内肿瘤微环境,也无法针对免疫治疗药物的作用机制反映出药物的靶点毒性。近年来,由于基因编辑技术及干细胞培养技术的不断进步,实验动物的人源化技术取得了巨大的进步。本文总结了目前可用于肿瘤免疫治疗药物研究的3种人源化动物模型(重建人免疫系统动物模型、重建人免疫系统+人源肿瘤组织异种移植动物模型和基因修饰的人源化动物模型)的特点和应用范围,希望为研究者在肿瘤免疫治疗药物临床前开发过程中选择合适的动物模型提供参考。
Immuno-oncology research has been intensified significantly in recent years due to the breakthrough development of tumor immunoregulation. In 2017, FDA approved two chimeric antigen receptor T-cell immunotherapies from Novartis and Kite, leading to rapid discoveries related to novel immune-oncology therapies. An ideal animal model for the preclinical evaluation of immuno-oncology drugs is one that can mimic the human tumor microenvironment. An appropriate animal model can be used for the preclinical safety and effectiveness evaluation, and will offer better predictability for clinical trials. With the development of gene editing and stem cell culture, the technology of humanized animal models has been rapidly progressing. This article attempts to review humanized animal models used for immuno-oncology research, and their applications.
作者
宋征
马璟
SONG Zheng;MA Jing(China State Institute of Pharmaceutical Industry,National Shanghai Center for New Drug Evaluation and Research,Shanghai Innostar Bio-Tech Co.,Ltd.,Shanghai 201203,China)
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2018年第3期161-167,共7页
Chinese Journal of Pharmacology and Toxicology
基金
上海市科学技术委员科研计划项目(15140901100)~~
