Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy

Mol Ther Methods Clin Dev. 2023 Sep 1:31:101104. doi: 10.1016/j.omtm.2023.08.023. eCollection 2023 Dec 14.

Abstract

Chimeric antigen receptor (CAR) T cells targeting CD19+ B cells have demonstrated efficacy in refractory systemic lupus erythematosus (SLE). Although initial clinical data suggest that anti-CD19 CAR T cell therapy is well tolerated and highly effective, the immunologic consequences of CAR T cell therapy in SLE patients remain unclear. We profiled serum in six refractory SLE patients prior to and 3 months following CAR T cell infusion. Three months post T cell infusion, the inflammatory cytokines IL-6 and TNFα decreased in patient sera. This was accompanied by elevations in serum IL-7 and BAFF. Furthermore, SLE-associated antibodies dropped profoundly in five of six patients. Last, consistent with other reports of CD19 CAR T therapy in B cell malignancies, we were able to show marginal impact of anti-CD19 CART therapy on pre-existing humoral immune responses in SLE patients. Together, these results provide insights into the mechanisms of efficacy of anti-CD19 CAR T cell therapy in SLE.

Keywords: CAR; SLE; antibodies; autoimmune disease; chimeric antigen receptor T cell; cytokines; systemic lupus erythematous; vaccines.