免疫系统人源化小鼠模型的建立应用及挑战.pdf

《中国医学前沿杂志 （电子版）》2017 年第9 卷第10 期 ● ●  15  重点号专题  DOI ：10.12037/YXQY.2017.10-03 免疫系统人源化小鼠模型的建立、应用 及挑战 李爽，邹建玲，鲁智豪，沈琳 （北京大学肿瘤医院暨北京市肿瘤防治研究所　消化肿瘤内科　恶性肿瘤发 病机制及转化研究教育部重点实验室，北京　100142 ） 【摘要】恶性肿瘤是威胁人类健康的主要因素之一，动物模型在临床前抗肿瘤药物评价体系中发挥重 要作用。但是目前常见的动物模型并不能很好地模拟患者的肿瘤微环境，尤其在免疫治疗的转化研究 中存在很大的局限性。因此，迫切需要建立具有人类免疫系统的动物模型来进行相关转化研究。免疫 系统人源化小鼠模型是指在免疫缺陷小鼠体内植入人的造血细胞、淋巴细胞或组织，使其具有人的免 疫功能的小鼠模型。在此基础上植入人的肿瘤细胞或肿瘤组织，可用于研究人类免疫系统环境下肿瘤 的生长情况、评估抗肿瘤治疗，尤其是免疫治疗效果及相关作用机制。 【关键词】免疫检查点抑制剂；免疫治疗 ；小鼠模型；人源化小鼠；肿瘤微环境 The establishment, application and challenge of the humanized mice LI Shuang, ZOU Jian-ling, LU Zhi-hao, SHEN Lin (Department of Gastrointestinal Oncology, Peking University Cancer Hospital Institute, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beij ing 100142, China) Corresponding author: SHEN Lin, E-mail: lin 100@ Abstract 【 】Cancer is a maj or burden of disease worldwide. Animal model plays an important role in the preclinical anti-tumor drug evaluation system. Despite the huge amount of advancement obtained from mouse studies, there are limitations to mouse models when investigating human biology. Several components of mouse biological systems are incongruent with those of humans, particularly their immune system. Animal models with human immune system are needed to mimicthe complexity of human tumor microenvironment. Humanized mice are defined as immunodeficient mice that have been engrafted with human hematopoietic cells, lymphocytes or tissues that generate a functional human immune system. Human tumor cells or tissue are engrafted in humanized mice to examine xenograft growth in the context of a human immune system, to assess the efficacy of immunotherapy and explore mechanisms. Key words 【 】Checkpo