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

• Published in: Molecular therapy. Methods & clinical development 2023-12, Vol.31, p.101104-101104, Article 101104
• Main Authors: Nunez, Daniel, Patel, Darshil, Volkov, Jenell, Wong, Steven, Vorndran, Zachary, Müller, Fabian, Aigner, Michael, Völkl, Simon, Mackensen, Andreas, Schett, Georg, Basu, Samik
• Format: Article
• Language: English
• Subjects: antibodies; autoimmune disease; Brief Report; CAR; chimeric antigen receptor T cell; cytokines; SLE; systemic lupus erythematous; vaccines
• ISSN: 2329-0501; 2329-0501
• DOI: 10.1016/j.omtm.2023.08.023

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. [Display omitted] CD19 CART therapy in SLE patients results in multiple serological changes. First, there is a decrease in the inflammatory cytokines IL-6 and TNFα. This is accompanied by elevations in serum IL-7 and BAFF. Furthermore, SLE-associated antibodies decrease in most patients. Last, there is a marginal impact on pre-existing humoral immunity.