INSERM U932, and SiRIC Translational Immunotherapy Team, Translational Research Department, Institut Curie, PSL Research University, Paris F-75005, France.
Maimónides Institute for Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain.
Trends Immunol. 2018 Sep;39(9):748-763. doi: 10.1016/j.it.2018.07.001. Epub 2018 Aug 2.
Immunotherapy is revolutionizing cancer treatment; however, complete responses are achieved in only a small fraction of patients and tumor types. Thus, there is an urgent need for predictive preclinical models to drive rational immunotherapeutic drug development, treatment combinations, and to minimize failures in clinical trials. Humanized mouse models (HIS) have been developed to study and modulate the interactions between immune components and tumors of human origin. In this review, we discuss recent advances in the 'humanization' of mouse models to improve the quality of human immune cell reconstitution. We also highlight new insights into the basic mechanisms, and provide a preclinical evaluation of onco-immunotherapies, as well as the limitations thereof, which constitute drivers for the improvement of the models to increase their translational power.
免疫疗法正在彻底改变癌症治疗方法;然而,只有一小部分患者和肿瘤类型能获得完全应答。因此,迫切需要预测性的临床前模型来推动合理的免疫治疗药物开发、治疗组合,并最大限度地减少临床试验的失败。已经开发了人源化小鼠模型 (HIS) 来研究和调节人类来源的免疫成分和肿瘤之间的相互作用。在这篇综述中,我们讨论了最近在小鼠模型“人源化”方面的进展,以提高人类免疫细胞重建的质量。我们还强调了对基本机制的新见解,并提供了对肿瘤免疫疗法的临床前评估,以及其局限性,这些都是改进模型以提高其转化能力的驱动力。