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抗CD19嵌合抗原受体T细胞(CART)疗法治疗后系统性红斑狼疮(SLE)患者的细胞因子及反应性概况

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

作者信息

Nunez Daniel, Patel Darshil, Volkov Jenell, Wong Steven, Vorndran Zachary, Müller Fabian, Aigner Michael, Völkl Simon, Mackensen Andreas, Schett Georg, Basu Samik

机构信息

Department of Computational Biology, Cabaletta Bio, Philadelphia, PA, USA.

Department of Protein and Molecular Biology, Cabaletta Bio, Philadelphia, PA, USA.

出版信息

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.

摘要

靶向CD19 B细胞的嵌合抗原受体(CAR)T细胞已在难治性系统性红斑狼疮(SLE)中显示出疗效。尽管初步临床数据表明抗CD19 CAR T细胞疗法耐受性良好且高效,但CAR T细胞疗法对SLE患者的免疫影响仍不清楚。我们对6例难治性SLE患者在CAR T细胞输注前和输注后3个月的血清进行了分析。T细胞输注后3个月,患者血清中的炎性细胞因子IL-6和TNFα减少。同时,血清IL-7和BAFF升高。此外,6例患者中有5例的SLE相关抗体大幅下降。最后,与其他关于CD19 CAR T疗法治疗B细胞恶性肿瘤的报道一致,我们能够证明抗CD19 CAR T疗法对SLE患者预先存在的体液免疫反应的影响很小。这些结果共同为抗CD19 CAR T细胞疗法治疗SLE的疗效机制提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2683/10514439/675c5ec8dc24/fx1.jpg

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