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Preclinical development of a humanized chimeric antigen receptor against B-cell maturation antigen for multiple myeloma
Pérez-Amill, Lorena (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Suñe, Guillermo (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Antoñana Vildosola, Asier (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Castella, Maria (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Najjar, Amer (Department of Pediatrics - Research. The University of Texas M. D. Anderson Cancer Center)
Bonet, Jaume (Laboratory of Protein Design and Immunoengineering. École Polytechnique Fédérale de Lausanne)
Fernández-Fuentes, Narcís (Universitat de Vic - Universitat Central de Catalunya)
Inogés, Susana (Clínica Universidad de Navarra)
López, Ascensión (Clínica Universidad de Navarra)
Bueno, Clara (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Juan, Manel (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Urbano Ispizua, Álvaro (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Martín-Antonio, B (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Universitat Autònoma de Barcelona

Date: 2021
Abstract: Multiple myeloma is a prevalent and incurable disease, despite the development of new and effective drugs. The recent development of chimeric antigen receptor (CAR)T cells has shown impressive results in the treatment of patients with relapsed or refractory hematologic B-cell malignancies. In recent years, B-cell maturation antigen (BCMA) has appeared as a promising antigen to target using a variety of immunotherapy treatments, including CART cells, for patients with multiple myeloma. To this end, we generated clinical-grade murine CART cells directed against BCMA, named ARI2m cells. Having demonstrated its efficacy, and in an attempt to avoid the immune rejection of CART cells by the patient, the single chain variable fragment was humanized, creating ARI2h cells. ARI2h cells showed comparable in vitro and in vivo efficacy to that of ARI2m cells, and superiority in cases of high tumor burden disease. In terms of inflammatory response, ARI2h cells produced less tumor necrosis factor-αand were associated with a milder in vivo toxicity profile. Large-scale expansion of both ARI2m and ARI2h cells was efficiently conducted following Good Manufacturing Practice guidelines, obtaining the target CART-cell dose required for treatment of multiple myeloma patients. Moreover, we demonstrated that soluble BCMA and BCMA released in vesicles both affect CAR-BCMA activity. In summary, this study sets the bases for the implementation of a clinical trial (EudraCT code: 2019-001472-11) to study the efficacy of ARI2h-cell treatment for patients with multiple myeloma.
Grants: Instituto de Salud Carlos III PI17-01043
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès
Document: Article ; recerca ; Versió publicada
Published in: Haematologica, Vol. 106 Núm. 1 (january 2021) , p. 173-184, ISSN 1592-8721

DOI: 10.3324/haematol.2019.228577
PMID: 31919085


12 p, 4.6 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
Articles > Research articles
Articles > Published articles

 Record created 2021-02-02, last modified 2023-12-04



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