CD19/BCMA-Targeted Chimeric Antigen Receptor-T Cell Therapy for Anti-HLA Antibody Sensitisation in Patients With...

Antibodies targeting foreign HLA molecules can be detrimental in transplantation. Nonetheless, existing desensitisation methods for anti-HLA antibodies frequently prove insufficient. We conducted a single-arm pilot study to evaluate CD19/B cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) cell therapy for desensitising anti-HLA antibodies prior to transplantation. Seven patients diagnosed with acute leukaemia participated in the study, comprising four individuals with acute myeloid leukaemia (AML) and three with acute B lymphoblastic leukaemia (B-ALL). Among them, one patient was treated with BCMA CAR-T cells, while six received CD19 CAR-T cells. No instances of neurotoxicity or severe cytokine release syndrome (grade ≥ 3) were noted. CAR-T cell expansion was observed in six patients (86%), with the exception of patient 3. Among the seven patients with pre-infusion anti-HLA-I antibodies, five (71%) showed a decrease in mean fluorescence intensity (MFI), including three (43%) who experienced a reduction greater than 75%. Among the six patients confirmed to exhibit CAR-T cell expansion in vivo, three presented with donor-specific anti-HLA antibodies (DSAs) prior to CAR-T cell infusion. The median MFI level of DSA declined from 15797.8 (7750.3-21106.0) to 3831.1 (523.3-13197.0) (p < 0.001) in the three patients studied. Two patients with decreased DSA levels after CD19 CAR-T cell infusion underwent combined desensitisation before haematopoietic stem cell transplantation. This pilot study illustrates the potential safety and efficacy of CD19 and BCMA CAR-T cells in desensitising anti-HLA antibodies in patients with AML or B-ALL. However, only one patient received BCMA CAR-T cells in our cohort, so further research with an expanded sample size is essential for comprehensively evaluating the safety and efficacy of CD19/BCMA CAR-T cell therapy for anti-HLA antibody sensitisation.