Immuno-engineering and Cellular Therapies
Ariadna Bartoló Ibars, n/a
PhD student
Department of Immunology, Centre de Diagnòstic Biomèdic, Hospital Clínic of Barcelona, Barcelona, Spain.
Cervera, Catalonia, Spain
Manel Juan, n/a
Head of Department
Department of Immunology, Centre de Diagnòstic Biomèdic, Hospital Clínic of Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain
Europa Azucena González Navarro, n/a
Department of Immunology, Centre de Diagnòstic Biomèdic, Hospital Clínic of Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain
Nela Klein González, n/a
Department of Immunology, Centre de Diagnòstic Biomèdic, Hospital Clínic of Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain
Berta Casanovas Albertí, n/a
Department of Immunology, Centre de Diagnòstic Biomèdic, Hospital Clínic of Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain
Valentín Ortiz Maldonado, n/a
Hematology Department, ICMHO, Hospital Clínic de Barcelona, Barcelona, Spain
Barcelona, Catalonia, Spain
Montserrat Torrebadell, n/a
Department of Hematology, Hospital Sant Joan de Déu (HSJD), Barcelona, Spain
Barcelona, Catalonia, Spain
Marta Español Rego, n/a
Immunology Department, Centre de Diagnòstic Biomèdic, Hospital Clínic de Barcelona, Barcelona, Spain
Barcelona, Catalonia, Spain
Maria Castellà, n/a
Department of Immunology, Centre de Diagnòstic Biomèdic, Hospital Clínic of Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain
Daniel Benítez, n/a
Department of Immunology, Centre de Diagnòstic Biomèdic, Hospital Clínic of Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain
Raquel Cabezón, n/a
Department of Immunology, Centre de Diagnòstic Biomèdic, Hospital Clínic of Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain
Jordi Esteve, n/a
Department of Hematology, ICMHO, Hospital Clinic de Barcelona, Spain
Barcelona, Catalonia, Spain
Jordi Yagüe, n/a
Department of Immunology, Centre de Diagnòstic Biomèdic, Hospital Clínic of Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain
Mariona Pascal, n/a
Department of Immunology, Centre de Diagnòstic Biomèdic, Hospital Clínic of Barcelona, Barcelona, Spain
Barcelona, Catalonia, Spain
Álvaro Urbano Ispizua, n/a
Department of Hematology, ICMHO, Hospital Clinic de Barcelona, Spain
Barcelona, Catalonia, Spain
Susana Rives, n/a
Department of Hematology, Hospital Sant Joan de Déu (HSJD), Barcelona, Spain
Barcelona, Catalonia, Spain
Julio Delgado, n/a
Hematology Department, ICMHO, Hospital Clínic de Barcelona, Barcelona, Spain
Barcelona, Catalonia, Spain
Background: ARI-0001 cells express a second generation CAR19, which combines the anti-CD19 scFv originated from A3B1, a murine monoclonal antibody, and intracellular domains. It has been approved for the treatment of acute lymphoblastic leukemia (ALL) in patients older than 25 years of age by the Spanish Agency of Medicine in 2021 under hospital exemption. Even though its safety and efficacy have been demonstrated, there is still lack of data about the relevance of the immunogenicity it triggers.
Methods: Regarding the humoral immune response, the presence of human anti-murine antibodies (HAMA) in patients’ sera was assessed at different time-points. Afterwards, cytotoxicity assays were performed to appraise whether these antibodies diminished the efficacy of ARI-0001 cells. About the cellular immunogenicity, CAR19 peptides were predicted in silico in relation to the HLA of the patients.
Results: A total of forty-seven patients received ARI-0001 cells. Approximately twenty-five per cent of the patients tested positive for the presence of anti-CAR antibodies a hundred days after the first or second infusion. Even though twenty-five per cent had anti-CAR antibodies, only some of them were diminishing the effectiveness of CAR-T19 in vitro. In relation to the prediction in silico, a set of 103 prioritized immunogenic peptides were selected to assess the T-cell response.
Conclusions: The presence of HAMA diminishes the efficacy of ARI-0001 cells in vitro and the most immunogenic peptides are derived from the scFv. So, these data suggest that the assessment of immunogenicity induced by CAR-T19 could be important, especially before considering a second infusion.
