Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/223052
Title: Bicistronic CAR-T Cell against BCMA and CD229 effectively controls myeloma even when BCMA expression is limited.
Author: Rodríguez Lobato, Luis Gerardo
Cardús Granell, Oriol
Mañé Pujol, Joan
Battram, Anthony M.
Vaqué Salsench, Sergi
Carpio Marmol, Judit
Pérez Amill, Lorena
Calderón, Hugo
Martín Antonio, Araceli Beatriz
Oliver Caldés, Aina
Lozano Garcia, Ester
Moreno Fajardo, David Fernando
Ortiz Maldonado, Valentín
Salas Gay, María Queralt
Daniel Bisbe, Anna de
Tovar Gomis, Natalia
Cibeira López, M. Teresa
Rosiñol Dachs, Laura
Bladé, J. (Joan)
Juan, Manel
Urbano Ispizua, Álvaro
Engel Rocamora, Pablo
Fernández de Larrea Rodríguez, Carlos José
Keywords: Mieloma múltiple
Teràpia cel·lular
Multiple myeloma
T cells
Issue Date: 2-Sep-2025
Publisher: American Association for Cancer Research
Abstract: Anti-BCMA CAR-T cell therapy has revolutionized the prognosis of relapsed / refractory multiple myeloma patients. Regrettably, despite unprecedented overall response rates achieved with this approach, most patients eventually relapse. One of the primary reasons for this is the complete loss or reduced expression of BCMA on the malignant plasma cell surface. Consequently, new therapeutic targets are under investigation. Another potential therapeutic approach involves the use of CAR-T cells targeting two tumor antigens. In this study, we developed and validated a monospecific CAR targeting CD229, which was effective in in vitro and in vivo NSG mouse models with both homogeneous and heterogeneous BCMA expression. Additionally, we created a bicistronic CAR-T cell targeting both CD229 and BCMA, which demonstrated efficacy in models with homogeneous BCMA expression, in heterogeneous models featuring small clonal populations with biallelic BCMA deletion, and in cases with reduced BCMA expression both in vivo and in vitro. Regarding "on-target off-tumor toxicity," no fratricide was observed among CAR-T cells, but there was a limited elimination of non-activated T-cells. The immune pressure exerted by anti-CD229 CAR-T cells led to the loss of the CD229 antigen expression in some instances. In summary, this work underscores the potential utility of CD229 alone or in combination with BCMA, as an immunotherapeutic target in multiple myeloma, especially in cases marked by diminished or absent BCMA expression.
Note: Versió postprint del document publicat a: https://doi.org/10.1158/2326-6066.CIR-24-1313
It is part of: Cancer Immunology Research, 2025, vol. 13, num. 9, p. 1374-1390
URI: https://hdl.handle.net/2445/223052
Related resource: https://doi.org/10.1158/2326-6066.CIR-24-1313
ISSN: 2326-6074
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Files in This Item:
File Description SizeFormat 
Manuscript CD229 CART CIR FINAL.pdf5.77 MBAdobe PDFView/Open    Request a copy


Embargat   Document embargat fins el 2-9-2026


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.