生成人源化小鼠中免疫治疗获得性耐药的患者来源异种移植模型的方案。

Protocol to generate a patient derived xenograft model of acquired resistance to immunotherapy in humanized mice.

机构信息

Preclinical Research Program, Vall d'Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain; Cancer Research Program, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain; Centro de Investigación Biomédica en Red de Cáncer, Monforte de Lemos, 08029 Madrid, Spain; Department of Biochemistry and Molecular Biology, Universitat Autónoma de Barcelona, Bellaterra, 08193 Barcelona, Spain.

Preclinical Research Program, Vall d'Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain.

出版信息

STAR Protoc. 2022 Oct 26;3(4):101712. doi: 10.1016/j.xpro.2022.101712. eCollection 2022 Dec 16.

DOI:10.1016/j.xpro.2022.101712

PMID:36317178

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9617204/

Abstract

Immunotherapy has revolutionized cancer treatment, but preclinical models are required to understand immunotherapy resistance mechanisms underlying patient relapse. This protocol describes how to generate an acquired resistance humanized model to immunotherapies in patient-derived xenografts (PDX). We detail steps to inject human CD34 cells into NSG mice, followed by generation of immunoresistant PDX in humanized mice. This approach recapitulates the human immune system, allowing investigators to generate preclinical resistance models to different immunotherapies for identifying the resistant phenotype. For complete details on the use and execution of this protocol, please refer to Martínez-Sabadell et al., 2022 and Arenas et al. (2021).

摘要

免疫疗法已经彻底改变了癌症治疗方法，但需要临床前模型来了解导致患者复发的免疫治疗耐药机制。本方案描述了如何在患者来源的异种移植物（PDX）中生成获得性耐药的人源化模型以进行免疫治疗。我们详细介绍了将人 CD34 细胞注入 NSG 小鼠的步骤，然后在人源化小鼠中生成免疫抵抗的 PDX。这种方法再现了人类免疫系统，使研究人员能够生成针对不同免疫疗法的临床前耐药模型，以鉴定耐药表型。有关本方案使用和执行的完整详细信息，请参阅 Martínez-Sabadell 等人，2022 年和 Arenas 等人。（2021 年）。