针对 CD19 靶向 CAR-T 细胞 varnimcabtagene autoleucel（ARI-0001）的 T 细胞应答：对免疫应答与治疗结局的启示

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.