Pos1432 car-tregs for systemic lupus erythematosus
Annals of the Rheumatic Diseases(2023)
摘要
Background Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by an abnormal inflammatory response against nuclear antigens with consequent tissue damage. Autoreactive B cells and auto-antibodies have a fundamental role in SLE pathogenesis. Regulatory T cells (Tregs) physiologically maintain the immune tolerance and are impaired in SLE. Polyclonal Treg trnasfer obtained unsatisfactory results due to the low number of disease-relevant antigen-specific cells. Chimeric Antigen Receptors (CARs) are molecules capable of redirecting T cell specificity. CAR-Tregs proved effective in pre-clinical mouse models of autoimmunity. Objectives We aimed at developing a CAR-Treg based product to be employed in SLE. Methods We isolated Tregs from Healthy Donors Peripheral Blood Mononuclear Cells (PBMCs) and expanded them with IL-2 and rapamycin. We transduced Tregs with a Lentiviral Vector encoding for a second-generation anti-CD19 CAR, considering the relevant role of autoreactive B cells and autoantibodies in SLE. Results Engineered cells retained their immune suppressive capabilities upon polyclonal stimulation. Noticeably, they acquired new antigen-specific suppressive capacities, being able to block autologous B cell proliferation. We set up a humanized mouse model of SLE. In vivo, CAR-Tregs delayed the occurrence of B cell lymphopenia, producing immunomodulatory cytokines and without showing toxicity or reprogramming towards Th17 pro-inflammatory cells. In inflamed organs, CAR-Tregs restored the normal composition of the immune system. Conclusion In conclusion, we efficiently generated anti-CD19 CAR-Tregs and proved their efficacy both in vitro and in an in vivo humanized mouse model of lupus. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.
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关键词
systemic lupus erythematosus,systemic lupus,car-tregs
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