Development of a Novel Anti-CD19 Chimeric Antigen Receptor: A Paradigm for an Affordable CAR T Cell Production at Academic Institutions
| Autor: | Ramon Vilella, Josep M. Canals, Miguel Caballero, Jaime Tabera, Raquel Martín-Ibáñez, Pablo Engel, Valentín Ortiz-Maldonado, Guillermo Suñe, Clara Bueno, Carles Serra-Pagès, Berta Marzal, Miquel Lozano, Julio Castaño, Europa Azucena González-Navarro, Susana Rives, Beatriz Martín-Antonio, Lorena Perez-Amill, Anna Boronat, Patricia Pérez-Galán, Joan Cid, Maria Castella, Julio Delgado, Pablo Menendez, Anna Vilarrodona, Daniel Benitez-Ribas, Alvaro Urbano-Ispizua, Esteve Trias, Olga Balagué, Jordi Yagüe, Elias Campo, Tycho Baumann, Vanina Rodriguez, Manel Juan |
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| Přispěvatelé: | Universitat de Barcelona |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Limfomes lcsh:QH426-470 T cell medicine.medical_treatment Immunoteràpia T cells lymphoma Immunotheraphy CD19 Article Viral vector 4-1BB 03 medical and health sciences 0302 clinical medicine Genetics medicine Cytotoxic T cell lcsh:QH573-671 preclinical studies Molecular Biology B cell Leukemia biology chimeric antigen receptor lcsh:Cytology business.industry leukemia Leucèmia Immunotherapy Chimeric antigen receptor 3. Good health lcsh:Genetics 030104 developmental biology medicine.anatomical_structure Cèl·lules T 030220 oncology & carcinogenesis Cancer research biology.protein Molecular Medicine Lymphomas immunotherapy business CD8 |
| Zdroj: | Molecular Therapy-Methods & Clinical Development r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol instname r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu Molecular Therapy. Methods & Clinical Development Molecular Therapy: Methods & Clinical Development, Vol 12, Iss, Pp 134-144 (2019) Dipòsit Digital de la UB Universidad de Barcelona Recercat. Dipósit de la Recerca de Catalunya r-FSJD: Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu Fundació Sant Joan de Déu |
| ISSN: | 2329-0501 |
| Popis: | Genetically modifying autologous T cells to express an anti-CD19 chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19+ B cell malignancies in several clinical trials (CTs). Making this treatment available to our patients prompted us to develop a novel CART19 based on our own anti-CD19 antibody (A3B1), followed by CD8 hinge and transmembrane region, 4-1BB- and CD3z-signaling domains. We show that A3B1 CAR T cells are highly cytotoxic and specific against CD19+ cells in vitro, inducing secretion of pro-inflammatory cytokines and CAR T cell proliferation. In vivo, A3B1 CAR T cells are able to fully control disease progression in an NOD.Cg-Prkdcscid Il2rdtm1Wjl/SzJ (NSG) xenograph B-ALL mouse model. Based on the pre-clinical data, we conclude that our CART19 is clearly functional against CD19+ cells, to a level similar to other CAR19s currently being used in the clinic. Concurrently, we describe the implementation of our CAR T cell production system, using lentiviral vector and CliniMACS Prodigy, within a medium-sized academic institution. The results of the validation phase show our system is robust and reproducible, while maintaining a low cost that is affordable for academic institutions. Our model can serve as a paradigm for similar institutions, and it may help to make CAR T cell treatment available to all patients. Keywords: chimeric antigen receptor, CD19, leukemia, lymphoma, immunotherapy, 4-1BB, T cell, preclinical studies |
| Databáze: | OpenAIRE |
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