T-cell responses against CD19-targeted CAR T cells varnimcabtagene autoleucel (ARI-0001): implications for immune response and therapy outcomes.
Por:
Bartoló-Ibars A, Aran A, Johansson AM, Ortiz-Maldonado V, Klein-González N, Alonso-Saladrigues A, James E, Urbano-Ispizua A, Rives-Solà S, Delgado J, González-Navarro EA, Kwok WW and Juan-Otero M
Publicada:
22 sep 2025
Ahead of Print:
22 sep 2025
Resumen:
Patients with B-cell malignancies receiving CD19-targeted chimeric antigen receptor (CAR) T-cell therapy may experience treatment failure due to various mechanisms. One significant factor is the host's immune response against the CAR-T product, mainly triggered by the immunogenicity of non-human sequences present in the CAR construct. In the CART19-BE-01 clinical trial (NCT03144583, ClinicalTrials.gov), patients with relapsed/refractory B-cell malignancies received treatment with varnimcabtagene autoleucel (ARI-0001 cells), a CD19-targeted autologous CAR-T product. During follow-up, both humoral and cellular immune responses were assessed against the extracellular domain of ARI-0001 cells, which was derived from the murine monoclonal antibody A3B1. Here, we report the case of a patient with B-cell acute lymphoblastic leukemia who required two infusions of ARI-0001 cells. Between the first and second CAR-T19 infusions, human antimurine antibodies were detected, which in vitro diminished the cytotoxicity of ARI-0001 cells against the CD19-positive NALM6 cell line. Furthermore, CD4(+) specific T cells against the CAR19 construct were isolated from the patient's peripheral blood mononuclear cells, showing recognition of the murine single-chain variable fragment peptides presented by human leukocyte antigen class II. This case underscores the need to monitor immune responses in patients before considering subsequent CAR-T infusions to preserve treatment efficacy.Trial registration number NCT03144583.
Filiaciones:
Bartoló-Ibars A:
Joint Platform of Immunotherapy Hospital Sant Joan de Déu (HSJD)-Hospital Clínic of Barcelona (HCB), Barcelona, Spain
Fundació de Recerca Clínic Barcelona - IDIBAPS, Barcelona, Spain
:
Joint Platform of Immunotherapy Hospital Sant Joan de Déu (HSJD)-Hospital Clínic of Barcelona (HCB), Barcelona, Spain
Fundació de Recerca Clínic Barcelona - IDIBAPS, Barcelona, Spain
Johansson AM:
Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA
Ortiz-Maldonado V:
Fundació de Recerca Clínic Barcelona - IDIBAPS, Barcelona, Spain
Department of Hematology, Hospital Clínic de Barcelona, Barcelona, Spain
Klein-González N:
Joint Platform of Immunotherapy Hospital Sant Joan de Déu (HSJD)-Hospital Clínic of Barcelona (HCB), Barcelona, Spain
Fundació de Recerca Clínic Barcelona - IDIBAPS, Barcelona, Spain
Alonso-Saladrigues A:
Leukemia and Lymphoma Department, Pediatric Cancer Center Barcelona HSJD, Barcelona, Spain
Institut de Recerca Sant Joan de Déu, Barcelona, Spain
University of Barcelona, Barcelona, Spain
James E:
Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA
Urbano-Ispizua A:
Fundació de Recerca Clínic Barcelona - IDIBAPS, Barcelona, Spain
Department of Hematology, Hospital Clínic de Barcelona, Barcelona, Spain
Department of Medicine, University of Barcelona, Barcelona, Spain
Rives-Solà S:
Leukemia and Lymphoma Department, Sant Joan de Deu Hospital, Barcelona, Spain
Sant Joan de Déu Research Institute, Barcelona, Spain
Delgado J:
Fundació de Recerca Clínic Barcelona - IDIBAPS, Barcelona, Spain
Department of Hematology, Hospital Clínic de Barcelona, Barcelona, Spain
University of Barcelona, Barcelona, Spain
González-Navarro EA:
Joint Platform of Immunotherapy Hospital Sant Joan de Déu (HSJD)-Hospital Clínic of Barcelona (HCB), Barcelona, Spain
Fundació de Recerca Clínic Barcelona - IDIBAPS, Barcelona, Spain
Department of Immunology, HCB, Barcelona, Spain
Kwok WW:
Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA
Juan-Otero M:
Joint Platform of Immunotherapy Hospital Sant Joan de Déu (HSJD)-Hospital Clínic of Barcelona (HCB), Barcelona, Spain
Fundació de Recerca Clínic Barcelona - IDIBAPS, Barcelona, Spain
University of Barcelona, Barcelona, Spain
Department of Immunology, HCB, Barcelona, Spain
Hosp Clin Barcelona HCB, Joint Platform Immunotherapy Hosp St Joan Deu
HSJD, Barcelona, Spain
Fundacio Recerca Clin Barcelona IDIBAPS, Barcelona, Spain
Benaroya Res Inst Virginia Mason, Seattle, WA USA
Hosp Clin Barcelona, Dept Hematol, Barcelona, Spain
Pediat Canc Ctr Barcelona HSJD, Leukemia & Lymphoma Dept, Barcelona,
Spain
Inst Recerca Sant Joan Deu, Barcelona, Spain
Univ Barcelona, Barcelona, Spain
Univ Barcelona, Dept Med, Barcelona, Spain
Sant Joan Deu Hosp, Leukemia & Lymphoma Dept, Barcelona, Spain
Sant Joan Deu Res Inst, Barcelona, Spain
HCB, Dept Immunol, Barcelona, Spain
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