免疫疗法彻底改变了癌症治疗,然而,并非所有肿瘤类型和患者都对这种方法有完全反应。建立预测性临床前模型将允许更准确和实用的免疫治疗药物开发。小鼠模型被广泛用作生物医学研究的体内系统。然而,由于啮齿动物和人类之间的显著差异,从小鼠模型到人类的大部分发现是不可能的。使用患者衍生的异种移植物的药理学开发和推进个性化医疗依赖于产生小鼠模型,其中鼠细胞和基因被它们的人类等同物取代。人源化小鼠(HM)提供了在人免疫系统背景下评估异种移植物生长的合适平台。在这次审查中,我们讨论了HM模型生成和应用的最新进展。我们还回顾了对基本机制的新见解,肿瘤免疫治疗的临床前评估,这些模型应用的当前局限性以及可用的改进策略。最后,我们指出了未来研究的一些问题。
Immunotherapy has revolutionized cancer treatment, however, not all tumor types and patients are completely responsive to this approach. Establishing predictive pre-clinical models would allow for more accurate and practical immunotherapeutic drug development. Mouse models are extensively used as in vivo system for biomedical research. However, due to the significant differences between rodents and human, it is impossible to translate most of the findings from mouse models to human. Pharmacological development and advancing personalized medicine using patient-derived xenografts relies on producing mouse models in which murine cells and genes are substituted with their human equivalent. Humanized mice (HM) provide a suitable platform to evaluate xenograft growth in the context of a human immune system. In this
review, we discussed recent advances in the generation and application of HM models. We also reviewed new insights into the basic mechanisms, pre-clinical evaluation of onco-immunotherapies, current limitations in the application of these models as well as available improvement strategies. Finally, we pointed out some issues for future studies.