接受 tisagenlecleucel 治疗的 B 细胞 ALL 儿科患者对 SARS-CoV-2 的强健免疫应答

Recipients of anti-CD19 targeted therapies such as chimeric antigen receptor (CAR)-T cell are considered at high risk for complicated Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection due to prolonged B cell aplasia and immunosuppression. These patients represent a unique cohort and so far, immune responses to SARS-CoV-2 have not been well characterized in this setting.

We report a pediatric patient with B-cell acute lymphoblastic leukemia (B-ALL) who had asymptomatic SARS-CoV-2 infection while receiving blinatumomab, followed by lymphodepletion (LD) and tisagenlecleucel, a CD19 targeting CAR-T therapy. The patient had a complete response to tisagenlecleucel, did not develop cytokine release syndrome, or worsening of SARS-CoV-2 during therapy. The patient had evidence of ongoing persistence of IgG antibody responses to spike and nucleocapsid after LD followed by tisagenlecleucel despite the B-cell aplasia.

Further we were able to detect SARS-CoV-2 specific T-cells recognizing multiple viral structural proteins for several months following CAR-T. The T-cell response was polyfunctional and predominantly CD4 restricted. This data has important implications for the understanding of SARS-CoV-2 immunity in patients with impaired immune systems and the potential application of SARS-CoV-2-specific T-cell therapeutics to treat patients with blood cancers who receive B cell depleting therapy.