{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:55:46Z","timestamp":1793156146524,"version":"4.5.0"},"reference-count":42,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"734","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2024,2,14]]},"abstract":"<jats:p>Multiple myeloma is the second most common hematological malignancy in adults and remains an incurable disease. B cell maturation antigen (BCMA)\u2013directed 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\u2013limiting 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.<\/jats:p>","DOI":"10.1126\/scitranslmed.adg7962","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T19:00:09Z","timestamp":1707937209000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":36,"title":["Engineered T cells secreting anti-BCMA T cell engagers control multiple myeloma and promote immune memory in vivo"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9545-6910","authenticated-orcid":true,"given":"Laura","family":"D\u00edez-Alonso","sequence":"first","affiliation":[{"name":"Cancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain."},{"name":"Immuno-Oncology and Immunotherapy Group, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain."},{"name":"H12O-CNIO Cancer Immunotherapy Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5040-2265","authenticated-orcid":true,"given":"A\u00efda","family":"Falgas","sequence":"additional","affiliation":[{"name":"Josep Carreras Leukaemia Research Institute, 08036 Barcelona, Spain."},{"name":"Red Espa\u00f1ola de Terapias Avanzadas (TERAV), Instituto de Salud Carlos III, 28029 Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1099-2018","authenticated-orcid":true,"given":"Javier","family":"Arroyo-R\u00f3denas","sequence":"additional","affiliation":[{"name":"Cancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain."},{"name":"Immuno-Oncology and Immunotherapy Group, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain."},{"name":"H12O-CNIO Cancer Immunotherapy Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6890-5883","authenticated-orcid":true,"given":"Paola A.","family":"Romenc\u00edn","sequence":"additional","affiliation":[{"name":"Josep Carreras Leukaemia Research Institute, 08036 Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7514-260X","authenticated-orcid":true,"given":"Alba","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Josep Carreras Leukaemia Research Institute, 08036 Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8816-9844","authenticated-orcid":true,"given":"Marina","family":"G\u00f3mez-Rosel","sequence":"additional","affiliation":[{"name":"Cancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain."},{"name":"Immuno-Oncology and Immunotherapy Group, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain."},{"name":"H12O-CNIO Cancer Immunotherapy Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5085-7756","authenticated-orcid":true,"given":"Bel\u00e9n","family":"Blanco","sequence":"additional","affiliation":[{"name":"Cancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain."},{"name":"Immuno-Oncology and Immunotherapy Group, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain."},{"name":"H12O-CNIO Cancer Immunotherapy Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain."},{"name":"Red Espa\u00f1ola de Terapias Avanzadas (TERAV), Instituto de Salud Carlos III, 28029 Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8229-1881","authenticated-orcid":true,"given":"Ana\u00efs","family":"Jim\u00e9nez-Reinoso","sequence":"additional","affiliation":[{"name":"Cancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain."},{"name":"Immuno-Oncology and Immunotherapy Group, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain."},{"name":"H12O-CNIO Cancer Immunotherapy Clinical Research Unit, Spanish National Cancer 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Salamanca, Spain."},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red-Oncolog\u00eda (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain."},{"name":"Biomedical Research Institute of Salamanca (IBSAL), 37007 Salamanca, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2435-8598","authenticated-orcid":true,"given":"\u00d3scar","family":"Aguilar-Sope\u00f1a","sequence":"additional","affiliation":[{"name":"Department of Immunology, Ophthalmology and ENT, School of Medicine, Universidad Complutense, 28040 Madrid, Spain."},{"name":"Lymphocyte Immunobiology Group, Instituto de Investigaci\u00f3n Sanitaria 12 de Octubre (imas12), 28041 Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3265-6878","authenticated-orcid":true,"given":"\u00c1ngel","family":"Ram\u00edrez-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Cancer Immunotherapy Unit 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Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3119-3218","authenticated-orcid":true,"given":"Laura","family":"Sanz","sequence":"additional","affiliation":[{"name":"Molecular Immunology Unit, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, 28222 Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1386-4943","authenticated-orcid":true,"given":"Eduardo","family":"Anguita","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical School, Universidad Complutense de Madrid, 28040 Madrid, Spain."},{"name":"Department of Hematology, IML, IdISSC, Hospital Cl\u00ednico San Carlos, 28040 Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7245-6977","authenticated-orcid":true,"given":"Antonio","family":"Valeri","sequence":"additional","affiliation":[{"name":"H12O-CNIO Hematological 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Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5424-5543","authenticated-orcid":true,"given":"Paula","family":"R\u00edo","sequence":"additional","affiliation":[{"name":"Red Espa\u00f1ola de Terapias Avanzadas (TERAV), Instituto de Salud Carlos III, 28029 Madrid, Spain."},{"name":"Division of Hematopoietic Innovative Therapies, Biomedical Innovation Unit, Centro de Investigaciones Energ\u00e9ticas Medioambientales y Tecnol\u00f3gicas (CIEMAT), 28040 Madrid, Spain."},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain."},{"name":"Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Universidad Aut\u00f3noma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manel","family":"Juan","sequence":"additional","affiliation":[{"name":"Red Espa\u00f1ola de 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Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0007-7230","authenticated-orcid":true,"given":"Alberto","family":"Orfao","sequence":"additional","affiliation":[{"name":"Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytometry Service (NUCLEUS), Universidad de Salamanca, 37007 Salamanca, Spain."},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red-Oncolog\u00eda (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain."},{"name":"Biomedical Research Institute of Salamanca (IBSAL), 37007 Salamanca, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9372-1007","authenticated-orcid":true,"given":"Pablo","family":"Men\u00e9ndez","sequence":"additional","affiliation":[{"name":"Josep Carreras Leukaemia Research Institute, 08036 Barcelona, Spain."},{"name":"Red Espa\u00f1ola de Terapias Avanzadas (TERAV), Instituto de Salud Carlos III, 28029 Madrid, 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