{
  "abstract": "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.",
  "authors": [
    {
      "affiliations": [
        "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"
      ],
      "name": "Ariadna Bartoló-Ibars"
    },
    {
      "affiliations": [
        "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"
      ],
      "name": "Andrea Aran"
    },
    {
      "affiliations": [
        "Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA"
      ],
      "name": "Alexandra M Johansson"
    },
    {
      "affiliations": [
        "Fundació de Recerca Clínic Barcelona - IDIBAPS, Barcelona, Spain",
        "Department of Hematology, Hospital Clínic de Barcelona, Barcelona, Spain"
      ],
      "name": "Valentín Ortiz-Maldonado"
    },
    {
      "affiliations": [
        "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"
      ],
      "name": "Nela Klein-González"
    },
    {
      "affiliations": [
        "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"
      ],
      "name": "Anna Alonso-Saladrigues"
    },
    {
      "affiliations": [
        "Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA"
      ],
      "name": "Eddie James"
    },
    {
      "affiliations": [
        "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"
      ],
      "name": "Alvaro Urbano-Ispizua"
    },
    {
      "affiliations": [
        "Leukemia and Lymphoma Department, Sant Joan de Deu Hospital, Barcelona, Spain",
        "Sant Joan de Deu Research Institute, Barcelona, Spain"
      ],
      "name": "Susana Rives"
    },
    {
      "affiliations": [
        "Fundació de Recerca Clínic Barcelona - IDIBAPS, Barcelona, Spain",
        "Department of Hematology, Hospital Clínic de Barcelona, Barcelona, Spain",
        "University of Barcelona, Barcelona, Spain"
      ],
      "name": "Julio Delgado"
    },
    {
      "affiliations": [
        "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"
      ],
      "name": "Europa Azucena González-Navarro"
    },
    {
      "affiliations": [
        "Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA"
      ],
      "name": "William W Kwok"
    },
    {
      "affiliations": [
        "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"
      ],
      "name": "Manel Juan"
    }
  ],
  "title": "T-cell responses against CD19-targeted CAR T cells varnimcabtagene autoleucel (ARI-0001): implications for immune response and therapy outcomes",
  "uid": "2ccd477f-b30d-5670-a99a-f26cda27c73a"
}