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用于评估免疫相关和抗癌药物递送系统的外周血单核细胞移植人源化小鼠模型

PBMC-engrafted humanized mice models for evaluating immune-related and anticancer drug delivery systems.

作者信息

Kametani Yoshie, Ito Ryoji, Manabe Yoshiyuki, Kulski Jerzy K, Seki Toshiro, Ishimoto Hitoshi, Shiina Takashi

机构信息

Department of Molecular Life Science, Division of Basic Medical Science, Tokai University School of Medicine, Isehara, Japan.

Institute of Advanced Biosciences, Tokai University, Hiratsuka, Japan.

出版信息

Front Mol Biosci. 2024 Aug 20;11:1447315. doi: 10.3389/fmolb.2024.1447315. eCollection 2024.

Abstract

Immune-related drug delivery systems (DDSs) in humanized mouse models are at the forefront of cancer research and serve as bridges between preclinical studies and clinical applications. These systems offer unique platforms for exploring new therapies and understanding their interactions with human cells and the immune system. Here, we focus on a DDS and a peripheral blood mononuclear cell (PBMC)-engrafted humanized mouse model that we recently developed, and consider some of the key components, challenges, and applications to advance these systems towards better cancer treatment on the basis of a better understanding of the immune response. Our DDS is unique and has a dual function, an anticancer effect and a capacity to fine-tune the immune reaction. The PBL-NOG-hIL-4-Tg mouse system is superior to other available humanized mouse systems for the development of such multifunctional DDSs because it supports the rapid reconstruction of an individual donor's immunity and avoids the onset of graft-versus-host disease.

摘要

人源化小鼠模型中的免疫相关药物递送系统(DDS)处于癌症研究的前沿,是临床前研究与临床应用之间的桥梁。这些系统为探索新疗法以及了解它们与人类细胞和免疫系统的相互作用提供了独特的平台。在此,我们重点关注我们最近开发的一种DDS和外周血单个核细胞(PBMC)植入的人源化小鼠模型,并考虑一些关键组成部分、挑战和应用,以便在更好地理解免疫反应的基础上推动这些系统实现更好的癌症治疗。我们的DDS具有独特性和双重功能,即抗癌作用和微调免疫反应的能力。PBL-NOG-hIL-4-Tg小鼠系统在开发此类多功能DDS方面优于其他现有的人源化小鼠系统,因为它支持快速重建个体供体的免疫力并避免移植物抗宿主病的发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64c8/11368775/bd4a8f5b15c8/fmolb-11-1447315-g001.jpg

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