Acquired cancer cell resistance to T cell bispecific antibodies and CAR T targeting HER2 through JAK2 down-modulation

Several mechanisms of resistance to T cell-engaging therapies have been described for solid tumors. Here, by using T cell bispecific antibodies and chimeric antigen receptors (CAR) T cells targeting HER2, the authors show that cancer cell intrinsic disruption of interferon-gamma signalling, includin...

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Main Authors:	Enrique J. Arenas, Alex Martínez-Sabadell, Irene Rius Ruiz, Macarena Román Alonso, Marta Escorihuela, Antonio Luque, Carlos Alberto Fajardo, Alena Gros, Christian Klein, Joaquín Arribas
Format:	Article
Language:	English
Published:	Nature Publishing Group 2021-02-01
Series:	Nature Communications
Online Access:	https://doi.org/10.1038/s41467-021-21445-4

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spelling	doaj-aa94e03a034246f68048ebc589ddfa652021-02-23T10:35:30ZengNature Publishing GroupNature Communications2041-17232021-02-0112111310.1038/s41467-021-21445-4Acquired cancer cell resistance to T cell bispecific antibodies and CAR T targeting HER2 through JAK2 down-modulationEnrique J. Arenas0Alex Martínez-Sabadell1Irene Rius Ruiz2Macarena Román Alonso3Marta Escorihuela4Antonio Luque5Carlos Alberto Fajardo6Alena Gros7Christian Klein8Joaquín Arribas9Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital CampusPreclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital CampusPreclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital CampusPreclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital CampusPreclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital CampusPreclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital CampusTumor Immunology & Immunotherapy Group, VHIO, Vall d’Hebron Barcelona Hospital CampusTumor Immunology & Immunotherapy Group, VHIO, Vall d’Hebron Barcelona Hospital CampusRoche Innovation Center Zurich, Roche Pharmaceutical Research and Early DevelopmentPreclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital CampusSeveral mechanisms of resistance to T cell-engaging therapies have been described for solid tumors. Here, by using T cell bispecific antibodies and chimeric antigen receptors (CAR) T cells targeting HER2, the authors show that cancer cell intrinsic disruption of interferon-gamma signalling, including downregulation of JAK2, confers resistance to T-cell mediated cytotoxicity.https://doi.org/10.1038/s41467-021-21445-4
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Enrique J. Arenas Alex Martínez-Sabadell Irene Rius Ruiz Macarena Román Alonso Marta Escorihuela Antonio Luque Carlos Alberto Fajardo Alena Gros Christian Klein Joaquín Arribas
spellingShingle	Enrique J. Arenas Alex Martínez-Sabadell Irene Rius Ruiz Macarena Román Alonso Marta Escorihuela Antonio Luque Carlos Alberto Fajardo Alena Gros Christian Klein Joaquín Arribas Acquired cancer cell resistance to T cell bispecific antibodies and CAR T targeting HER2 through JAK2 down-modulation Nature Communications
author_facet	Enrique J. Arenas Alex Martínez-Sabadell Irene Rius Ruiz Macarena Román Alonso Marta Escorihuela Antonio Luque Carlos Alberto Fajardo Alena Gros Christian Klein Joaquín Arribas
author_sort	Enrique J. Arenas
title	Acquired cancer cell resistance to T cell bispecific antibodies and CAR T targeting HER2 through JAK2 down-modulation
title_short	Acquired cancer cell resistance to T cell bispecific antibodies and CAR T targeting HER2 through JAK2 down-modulation
title_full	Acquired cancer cell resistance to T cell bispecific antibodies and CAR T targeting HER2 through JAK2 down-modulation
title_fullStr	Acquired cancer cell resistance to T cell bispecific antibodies and CAR T targeting HER2 through JAK2 down-modulation
title_full_unstemmed	Acquired cancer cell resistance to T cell bispecific antibodies and CAR T targeting HER2 through JAK2 down-modulation
title_sort	acquired cancer cell resistance to t cell bispecific antibodies and car t targeting her2 through jak2 down-modulation
publisher	Nature Publishing Group
series	Nature Communications
issn	2041-1723
publishDate	2021-02-01
description	Several mechanisms of resistance to T cell-engaging therapies have been described for solid tumors. Here, by using T cell bispecific antibodies and chimeric antigen receptors (CAR) T cells targeting HER2, the authors show that cancer cell intrinsic disruption of interferon-gamma signalling, including downregulation of JAK2, confers resistance to T-cell mediated cytotoxicity.
url	https://doi.org/10.1038/s41467-021-21445-4
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Acquired cancer cell resistance to T cell bispecific antibodies and CAR T targeting HER2 through JAK2 down-modulation

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