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dc.contributor.author | Díez-Alonso, Laura | |
dc.contributor.author | Falgas, Aïda | |
dc.contributor.author | Arroyo-Ródenas, Javier | |
dc.contributor.author | Romencín, Paola A | |
dc.contributor.author | Martínez, Alba | |
dc.contributor.author | Gómez-Rosel, Marina | |
dc.contributor.author | Blanco, Belén | |
dc.contributor.author | Jiménez-Reinoso, Anaïs | |
dc.contributor.author | Mayado, Andrea | |
dc.contributor.author | Pérez-Pons, Alba | |
dc.contributor.author | Aguilar-Sopeña, Óscar | |
dc.contributor.author | Ramírez-Fernández, Ángel | |
dc.contributor.author | Segura-Tudela, Alejandro | |
dc.contributor.author | Perez-Amill, Lorena | |
dc.contributor.author | Tapia-Galisteo, Antonio | |
dc.contributor.author | Domínguez-Alonso, Carmen | |
dc.contributor.author | Rubio-Pérez, Laura | |
dc.contributor.author | Jara, Maria | |
dc.contributor.author | Solé, Francesc | |
dc.contributor.author | Hangiu, Oana | |
dc.contributor.author | Almagro, Laura | |
dc.contributor.author | Albitre, Ángela | |
dc.contributor.author | Penela, Petronila | |
dc.contributor.author | Sanz, Laura | |
dc.contributor.author | Anguita, Eduardo | |
dc.contributor.author | Valeri, Antonio | |
dc.contributor.author | García-Ortiz, Almudena | |
dc.contributor.author | Río, Paula | |
dc.contributor.author | Juan, Manel | |
dc.contributor.author | Martínez-López, Joaquín | |
dc.contributor.author | Roda-Navarro, Pedro | |
dc.contributor.author | Martín-Antonio, Beatriz | |
dc.contributor.author | Orfao, Alberto | |
dc.contributor.author | Menéndez, Pablo | |
dc.contributor.author | Bueno, Clara | |
dc.contributor.author | Álvarez-Vallina, Luis | |
dc.contributor.author | Álvarez-Vallina, Luis | |
dc.date.accessioned | 2024-02-16T11:27:58Z | |
dc.date.available | 2024-02-16T11:27:58Z | |
dc.date.issued | 2024-02-14 | |
dc.identifier.citation | Sci Transl Med . 2024 ;16(734):eadg7962. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/18209 | |
dc.description.abstract | Multiple myeloma is the second most common hematological malignancy in adults and remains an incurable disease. B cell maturation antigen (BCMA)-directed immunotherapy, including T cells bearing chimeric antigen receptors (CARs) and systemically injected bispecific T cell engagers (TCEs), has shown remarkable clinical activity, and several products have received market approval. However, despite promising results, most patients eventually become refractory and relapse, highlighting the need for alternative strategies. Engineered T cells secreting TCE antibodies (STAb) represent a promising strategy that combines the advantages of adoptive cell therapies and bispecific antibodies. Here, we undertook a comprehensive preclinical study comparing the therapeutic potential of T cells either expressing second-generation anti-BCMA CARs (CAR-T) or secreting BCMAxCD3 TCEs (STAb-T) in a T cell-limiting experimental setting mimicking the conditions found in patients with relapsed/refractory multiple myeloma. STAb-T cells recruited T cell activity at extremely low effector-to-target ratios and were resistant to inhibition mediated by soluble BCMA released from the cell surface, resulting in enhanced cytotoxic responses and prevention of immune escape of multiple myeloma cells in vitro. These advantages led to robust expansion and persistence of STAb-T cells in vivo, generating long-lived memory BCMA-specific responses that could control multiple myeloma progression in xenograft models, outperforming traditional CAR-T cells. These promising preclinical results encourage clinical testing of the BCMA-STAb-T cell approach in relapsed/refractory multiple myeloma. | es_ES |
dc.description.sponsorship | Acknowledgments: We would like to thank the cell Sorting Service of the nUcleUS platform (University of Salamanca, Salamanca, Spain) for technical assistance. Funding: Financial support for this work was obtained from the Spanish Ministry of Science and innovation Mcin/Aei/10.13039/501100011033 (PiD2020- 115444GB- i00 to P.r.- n., PiD2019- 108160rB- i00 to P.M., Ple2021- 0075 to c.B., and PiD2020- 117323rB- 100 and PDc2021- 121711- 100 to l.Á.-V.), partially supported by the european regional Development Fund (erDF); the carlos iii health institute (iSciii) (Pi20/01030 to B.B., Pi19/00132 to l.S., Pi21- 01834 to P.P., Pi20/00822 to c.B., and DTS20/00089 to l.Á.-V.), partially supported by the erDF; the iSciii- ricorS within the next Generation eU program (plan de recuperación, Transformación y resilencia) (rD21/0017/0030 to B.B. and J.M.- l. and rD21/0017/0029 to P.M.); the iSciii- ciBeronc program (cB16/12/00400 to A.o.), the criS cancer Foundation (FcriS- 2021- 001 to J.M.- l. and FcriS- 2021- 0090 to l.Á.-V.), the Spanish Association Against cancer (Aecc) (PrYGn234975Mene to P.M., PrYGn211192BUen to c.B., and ProYe19084AlVA and PrYGn234844AlVA to l.Á.-V.); the Accelerator Award- cancer research UK/Airc/Aecc- incAr (GeAcc18001orF to A.o.), the Fundación “la caixa” (lcF/Pr/hr19/52160011 to P.M. and hr21- 00761 project il7r_lungcan to l.Á.-V.), the european research council (erc) (erc- Poc- 957466 to P.M.) and erc under the eU’s horizon Program (grant agreement 101100665 to P.M.), the Fundación de investigación Biomédica 12 de octubre (programa investiga 2022- 0082) to l.Á.-V.; the Fundación ramón Areces to P.P. l.D.-A. was supported by a rio hortega fellowship from the carlos iii health institute (cM20/00004). A.F. was supported by a postdoctoral fellowship from the Spanish Ministry of Science and innovation (FJc2021- 046789- i). A. Mayado was supported by the ciBeronc (PrF- 2869). A.P.- P. was supported by a grant from the Government of castilla y león (orden eDU/556/2019; Valladolid, Spain). M.G.- r. was supported by an industrial PhD ellowship from the comunidad de Madrid (inD2022/BMD- 23732). o.A.- S. was supported by a PhD fellowship from the complutense University of Madrid. c.D.-A. was supported by a PhD fellowship from the Spanish Ministry of Science and innovation (Pre2018- 083445). l.r.- P. was supported by a PhD fellowship from the immunology chair, Universidad Francisco de Vitoria/Merck. o.h. was supported by an industrial PhD fellowship from the comunidad de Madrid (inD2020/BMD- 17668). A.V. is supported by research institute hospital 12 de octubre (imas12). A.G.- o. is supported by hiGeA 2019/0123 Aie project to J.M.- l. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | National Academy of Sciences | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject.mesh | Multiple Myeloma | es_ES |
dc.subject.mesh | Receptors, Chimeric Antigen | es_ES |
dc.subject.mesh | Adult | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | T-Lymphocytes | es_ES |
dc.subject.mesh | Immunotherapy, Adoptive | es_ES |
dc.subject.mesh | B-Cell Maturation Antigen | es_ES |
dc.subject.mesh | Immunologic Memory | es_ES |
dc.subject.mesh | Neoplasm Recurrence, Local | es_ES |
dc.title | Engineered T cells secreting anti-BCMA T cell engagers control multiple myeloma and promote immune memory in vivo. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 38354229 | es_ES |
dc.format.volume | 16 | es_ES |
dc.format.number | 734 | es_ES |
dc.format.page | eadg7962 | es_ES |
dc.identifier.doi | 10.1126/scitranslmed.adg7962 | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | es_ES |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.contributor.funder | Asociación Española Contra el Cáncer | es_ES |
dc.contributor.funder | Fundación La Caixa | es_ES |
dc.contributor.funder | Fundación Ramón Areces | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea. European Research Council (ERC) | es_ES |
dc.contributor.funder | Research Institute Hospital 12 de Octubre | es_ES |
dc.contributor.funder | CRIS contra el Cáncer | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1946-6242 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1126/scitranslmed.adg7962. | es_ES |
dc.identifier.journal | Science translational medicine | es_ES |
dc.repisalud.institucion | CNIO | es_ES |
dc.rights.accessRights | open access | es_ES |