PO.TB04.02 · 肿瘤生物学
利用人源化小鼠增强免疫肿瘤学中的临床前见解
Enhancing preclinical insights in immuno-oncology with humanized mice
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
肿瘤微环境内的免疫细胞越来越被认为是癌症治疗的关键靶点。然而,由于根本性的物种间差异,来自传统动物模型的发现往往无法有效转化到人类。这一局限推动了人源化小鼠模型的发展,这些模型能够更准确地再现人类免疫生物学并支持新兴免疫治疗策略的临床前评估。
为在免疫缺陷小鼠中重建功能性的人类免疫系统,研究人员通常移植人外周血单个核细胞(PBMCs)或造血干细胞(HSCs)。这些人源化小鼠模型使得能够在体内研究人类免疫细胞的发育、活化和肿瘤-免疫相互作用,弥补了传统同基因模型无法解决的关键空白。当与人肿瘤细胞系或患者来源异种移植物的植入相结合时,人源化小鼠为评估广泛的肿瘤治疗策略提供了一个独特相关的平台,包括过继性免疫细胞疗法、免疫检查点抑制剂和溶瘤病毒。
在这项工作中,我们展示了皮下和播散性静脉人源化肿瘤模型的肿瘤生长动态和免疫分析结果。概述了纳入肿瘤负荷和免疫细胞移植的随机化策略,以增强实验的稳健性。详细说明了捕捉免疫调节和抗肿瘤疗效的关键读出指标。
示例数据集和案例研究展示了这些平台在免疫肿瘤学候选药物临床前评估中的多功能性和转化价值。总体而言,这些发现凸显了人源化小鼠作为连接发现研究与临床开发的强大桥梁。
查看英文原文 English abstract
Immune cells within the tumor microenvironment are increasingly recognized as critical targets for cancer therapy. However, findings from conventional animal models often fail to translate effectively to humans due to fundamental interspecies differences. This limitation has driven the development of humanized mouse models capable of more accurately recapitulating human immune biology and supporting the preclinical evaluation of emerging immunotherapeutic strategies.
To recreate a functional human immune system in immunodeficient mice, researchers commonly engraft either human peripheral blood mononuclear cells (PBMCs) or hematopoietic stem cells (HSCs). These humanized mouse models enable the study of human immune cell development, activation, and tumor-immune interactions in vivo, addressing key gaps that traditional syngeneic models cannot. When coupled with the implantation of human tumor cell lines or patient-derived xenografts, humanized mice provide a uniquely relevant platform for assessing a broad spectrum of oncological therapeutic strategies, including adoptive immune cell therapies, immune checkpoint inhibitors, and oncolytic viruses.
In this work, we present tumor growth dynamics and immune profiling outcomes across both subcutaneous and disseminated intravenous humanized tumor models. Randomization strategies incorporating tumor burden and immune cell engraftment are outlined to enhance experimental robustness. Key readouts capturing immune modulation and antitumor efficacy are detailed.
Illustrative datasets and case studies demonstrate the versatility and translational value of these platforms for preclinical assessment of immune-oncology drug candidates. Overall, the findings highlight humanized mice as a powerful bridge between discovery research and clinical development.
利益披露 Disclosure
C. Mignard, None..
Z. Perin, None..
E. Verronese, None..
D. France, None..
V. Faugeroux, None..
M. Hillairet de Boisferon, None.