Dysregulated B-cell activation plays pivotal roles in systemic lupus erythematosus(SLE),which makes B-cell depletion a potential strategy for SLE treatment.The clinical success of anti-CD19 CAR-T cells in treating B-c...Dysregulated B-cell activation plays pivotal roles in systemic lupus erythematosus(SLE),which makes B-cell depletion a potential strategy for SLE treatment.The clinical success of anti-CD19 CAR-T cells in treating B-cell malignancies has attracted the attention of researchers.In this study,we aimed to investigate the feasibility of applying anti-CD19 CAR-T cell therapy to SLE treatment in a mouse disease model.We constructed murine anti-CD19 CARs with either CD28 or 4-1BB as the intracellular costimulatory motif and evaluated the therapeutic function of the corresponding CAR-T cells by infusing them into MRL-lpr mice.Furthermore,anti-CD19 CAR-T cells were transferred to MRL-lpr mice before the onset of disease to determine their role in SLE prevention.According to our observations,compared with antibody treatment,the adoptive transfer of our anti-CD19 CAR-T cells showed a more sustained B-cell-depletion effect in MRL-lpr mice.The transfer of syngeneic anti-CD19 CAR-T cells not only prevented disease pathogenesis before the onset of disease symptoms but also displayed therapeutic benefits at a later stage after disease progression.We also tried to optimize the treatment strategy and found that compared with CAR-T cells with the CD28 costimulatory motif,CAR-T cells with the 4-1BB costimulatory motif showed better therapeutic efficiency without cell enrichment.Taken together,these results show that anti-CD19 CAR-T cell therapy was effective in the prevention and treatment of a murine model of SLE,indicating its potential for clinical use in patients.展开更多
In a recent study from NEJM,Mougiakakos et al.reported a case in which autologous anti-CD19 CAR-T cell therapy was used in the treatment of a refractory SLE patient[1].Rapid remission of severe SLE was observed in thi...In a recent study from NEJM,Mougiakakos et al.reported a case in which autologous anti-CD19 CAR-T cell therapy was used in the treatment of a refractory SLE patient[1].Rapid remission of severe SLE was observed in this case,indicating the potential of application of B cell-targeting CAR-T cell therapy in severe autoimmune diseases.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China(31770954,31530019 to L.L.and 31900628 to Q.X.)the Fundamental Research Funds for the Central Universities(2018XZZX001-12 to L.L.).
文摘Dysregulated B-cell activation plays pivotal roles in systemic lupus erythematosus(SLE),which makes B-cell depletion a potential strategy for SLE treatment.The clinical success of anti-CD19 CAR-T cells in treating B-cell malignancies has attracted the attention of researchers.In this study,we aimed to investigate the feasibility of applying anti-CD19 CAR-T cell therapy to SLE treatment in a mouse disease model.We constructed murine anti-CD19 CARs with either CD28 or 4-1BB as the intracellular costimulatory motif and evaluated the therapeutic function of the corresponding CAR-T cells by infusing them into MRL-lpr mice.Furthermore,anti-CD19 CAR-T cells were transferred to MRL-lpr mice before the onset of disease to determine their role in SLE prevention.According to our observations,compared with antibody treatment,the adoptive transfer of our anti-CD19 CAR-T cells showed a more sustained B-cell-depletion effect in MRL-lpr mice.The transfer of syngeneic anti-CD19 CAR-T cells not only prevented disease pathogenesis before the onset of disease symptoms but also displayed therapeutic benefits at a later stage after disease progression.We also tried to optimize the treatment strategy and found that compared with CAR-T cells with the CD28 costimulatory motif,CAR-T cells with the 4-1BB costimulatory motif showed better therapeutic efficiency without cell enrichment.Taken together,these results show that anti-CD19 CAR-T cell therapy was effective in the prevention and treatment of a murine model of SLE,indicating its potential for clinical use in patients.
基金Our work was supported by grants from the National Natural Science Foundation of China(31930038,31770954,and 31530019 to LL).
文摘In a recent study from NEJM,Mougiakakos et al.reported a case in which autologous anti-CD19 CAR-T cell therapy was used in the treatment of a refractory SLE patient[1].Rapid remission of severe SLE was observed in this case,indicating the potential of application of B cell-targeting CAR-T cell therapy in severe autoimmune diseases.
