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Updated: Aug 23, 2025
Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors
Published on: December 16, 2022
Protocol to generate a patient derived xenograft model of acquired resistance to immunotherapy in humanized mice
Alex Martínez-Sabadell1, Pablo Ovejero Romero2, Joaquín Arribas3
1Preclinical 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.
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 in vivo 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).
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 in vivo 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).
