The target antigen determines the mechanism of acquired resistance to T cell-based therapies
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- dc.contributor.author Martínez Sabadell, Alex
- dc.contributor.author Morancho Armisen, Beatriz
- dc.contributor.author Rius Ruiz, Irene
- dc.contributor.author Román Alonso, Macarena
- dc.contributor.author Ovejero Romero, Pablo
- dc.contributor.author Escorihuela, Marta
- dc.contributor.author Chicote, Irene
- dc.contributor.author Palmer, Héctor G.
- dc.contributor.author Nonell Mazelon, Lara, 1972-
- dc.contributor.author Alemany-Chavarria, Mercè
- dc.contributor.author Klein, Christian
- dc.contributor.author Bacac, Marina
- dc.contributor.author Arribas, Joaquín
- dc.contributor.author Arenas, Enrique J.
- dc.date.accessioned 2023-01-26T07:31:21Z
- dc.date.available 2023-01-26T07:31:21Z
- dc.date.issued 2022
- dc.description.abstract Despite the revolution of immunotherapy in cancer treatment, patients eventually progress due to the emergence of resistance. In this scenario, the selection of the tumor antigen can be decisive in the success of the clinical response. T cell bispecific antibodies (TCBs) are engineered molecules that include binding sites to the T cell receptor and to a tumor antigen. Using gastric CEA+/HER2+ MKN45 cells and TCBs directed against CEA or HER2, we show that the mechanism of resistance to a TCB is dependent on the tumor antigen. Acquired resistant models to a high-affinity-CEA-targeted TCB exhibit a reduction of CEA levels due to transcriptional silencing, which is reversible upon 5-AZA treatment. In contrast, a HER2-TCB resistant model maintains HER2 levels and exhibit a disruption of the interferon-gamma signaling. These results will help in the design of combinatorial strategies to increase the efficacy of cancer immunotherapies and to anticipate and overcome resistances.
- dc.format.mimetype application/pdf
- dc.identifier.citation Martínez-Sabadell A, Morancho B, Rius Ruiz I, Román Alonso M, Ovejero Romero P, Escorihuela M, et al. The target antigen determines the mechanism of acquired resistance to T cell-based therapies. Cell Rep. 2022 Oct 18; 41(3): 111430. DOI: 10.1016/j.celrep.2022.111430
- dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2022.111430
- dc.identifier.issn 2211-1247
- dc.identifier.uri http://hdl.handle.net/10230/55440
- dc.language.iso eng
- dc.publisher Elsevier
- dc.rights This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
- dc.subject.keyword 5-AZA
- dc.subject.keyword CEA
- dc.subject.keyword CP
- dc.subject.keyword Cancer
- dc.subject.keyword HER2
- dc.subject.keyword T cell bispecific antibody
- dc.subject.keyword Antigen
- dc.subject.keyword Immunotherapy
- dc.subject.keyword Interferon-gamma patient-derived xenografts
- dc.subject.keyword Resistance
- dc.title The target antigen determines the mechanism of acquired resistance to T cell-based therapies
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion