肿瘤免疫研究中常用的小鼠模型

Mouse models commonly used in immuno-oncology therapy

肿瘤免疫(IO)治疗已成为肿瘤治疗研究领域的热点,并在多个适应证中取得了革命性的突破。针对IO产品开发的基础研究和临床试验取得了较大的进展,但也面临许多转化医学方面的挑战,其中动物实验对人体免疫相关不良反应的预测性较差是最为突出的问题。特定免疫表型的小鼠模型能在一定程度上模拟肿瘤患者的系统免疫状态和肿瘤微环境,因而广泛应用于IO候选分子的非临床有效性和安全性研究。本文简略回顾了目前IO研究中常用的小鼠模型,着重对免疫检查点药物研究中常用的小鼠模型进行分析,并提出相关非临床研究的建议,供读者交流和讨论。

Immuno-oncology(IO) therapy is a hot spot in cancer treatment, and has made revolutionary breakthrough in various indications. Basic research and clinical trials for IO product development have made great progress, while more challenges still exist in the translation to clinical practice. The poor predictability for immune-related adverse effects in humans through animal studies is a prominent issue. The mouse model with specific immunophenotype may mimic the systemic immune status and tumor microenvironment of patients to a certain extent, and has been widely used in non-clinical efficacy and safety studies of IO therapeutics. This paper briefly reviewed the current mouse models commonly used in IO research, focused on the comparison/analysis of the mouse models in the development of immune checkpoint regulatory drug candidates, and put forward suggestions on related non-clinical research.