Protocol to generate a patient derived xenograft model of acquired resistance to immunotherapy in humanized mice
Martínez-Sabadell, Alex (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Ovejero Romero, Pablo (Vall d'Hebron Institut d'Oncologia)
Arribas, Joaquín V. (Vall d'Hebron Institut d'Oncologia)
Arenas, Enrique J. (Centro de Investigación Biomédica en Red de Cáncer)

Date:	2022
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 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 and . Publisher's note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics. 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.
Grants:	Instituto de Salud Carlos III PI19/01181
Note:	Altres ajuts: Asociación Española Contra el Cancer (GCAEC19017ARRI); Breast Cancer Research Foundation (BCRF-21-008); AECC (POSTD211413AREN); Cancer Immunology and Immunotherapy (CAIMI-2) program funded by BBVA Foundation; Spanish Government (PFIS FI20/00188)
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Cell isolation ; Cancer ; Health sciences ; Immunology ; Model organisms ; Stem cells
Published in:	STAR Protocols, Vol. 3, Issue 4 (December 2022) , art. 101712, ISSN 2666-1667

DOI: 10.1016/j.xpro.2022.101712
PMID: 36317178

15 p, 2.9 MB

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