人源化小鼠在肿瘤免疫治疗研究中的应用

The Application of Humanized Mice Models in Tumor Immunotherapy Research

随着肿瘤免疫学的快速发展,肿瘤的免疫治疗已成为肿瘤药物开发中的一个热点领域。然而,由于哺乳动物间免疫系统的种属差异性,现有的动物模型不能准确地预测人类免疫系统与肿瘤的相互作用。许多在临床前动物模型中具有良好治疗效果的抗肿瘤药物在肿瘤患者体内却不能发挥相应的药效。因此,肿瘤免疫治疗药物的临床前评价亟需合适的动物模型。人源化小鼠是通过将人源细胞或组织移植到免疫缺陷小鼠体内构建的小鼠模型。与传统动物模型相比,人免疫系统(Human immune system,HIS)小鼠、人免疫系统肿瘤(Human immune system tumor mice,HTM)小鼠、患者来源的异种移植肿瘤(Patient-derived xenograft tumor,PDX)小鼠、和人免疫系统PDX小鼠等人源化小鼠模型能够较好的模拟人免疫系统和患者的肿瘤微环境,为肿瘤免疫治疗的体内研究提供了可靠地平台。文章主要对免疫缺陷小鼠的发展和不同人源化小鼠的构建以及在肿瘤治疗研究中的应用作一综述。

With the rapid development of tumor immunology,tumor immunotherapy has become a hot research areas of oncology drugs development. However,the immune system of mammalian is species specific,and the existing animal models cannot accurately predict the interaction between human immune system and the tumors. Many anti-cancer drugs with good therapeutic effects are in preclinical animal models,but can＇t play the corresponding efficacy when given to cancer patients. Therefore,there is a growing need for animal models to carry out preclinical evaluation of tumor immunotherapy. Humanized mice are defined as immunodeficient mice engrafted with human cells or tissues. Compared with traditional animal models,humanized mouse models such as human immune system（HIS） mice,human immune system tumor（HTM） mice,patient-derived xenograft tumor（PDX） mice and human immune system PDX mice can better simulate human immune system and the patient＇s tumor microenvironment,thus providing reliable platforms for the in vivo research of tumor immunotherapy. The development of immunodeficient mice and the construction of different types of humanized mice and their applications in the immunotherapy of tumors have been reviewed in this paper.