Developing universal CARs with improved flexible targeting and controllable activities is urgently needed.While several studies have suggested the potential of CD16a in tandem with monoclonal antibodies to construct u...Developing universal CARs with improved flexible targeting and controllable activities is urgently needed.While several studies have suggested the potential of CD16a in tandem with monoclonal antibodies to construct universal CAR-T cells,the weak affinity between them is one of the limiting factors for efficacy.Herein,we systematically investigated the impact of Fcγreceptor(FcγR)affinity on CAR-T cells properties by constructing universal CARs using Fcγreceptors with different affinities for IgG1 antibodies,namely CD16a,CD32a,and CD64.We demonstrated that the activities of these universal CAR-T cells on tumor cells could be redirected and regulated by IgG1 antibodies.In xenografted mice,64CAR chimeric Jurkat cells with the highest affinity showed significant antitumor effects in combination with herceptin in the HER2 low expression U251 MG model.However,in the CD20 high expression Raji model,64CAR caused excessive activation of CAR-T cells,which resulted in cytokine release syndrome(CRS)and the decline of antitumor activity,and 32CAR with a moderate affinity brought the best efficacy.Our work extended the knowledge about FcγR-based universal CAR-T cells and suggested that only the FcγRCAR with an appropriate affinity can offer the optimal antitumor advantages of CAR-T cells.展开更多
Objective:To investigate the correlation of serum P2X7 receptor, CD64 and CD54 expression with infection process in children with bacterial pneumonia.Methods: A total of 164 children with bacterial pneumonia hospitali...Objective:To investigate the correlation of serum P2X7 receptor, CD64 and CD54 expression with infection process in children with bacterial pneumonia.Methods: A total of 164 children with bacterial pneumonia hospitalized in this hospital between June 2016 and February 2018 were selected as bacterial pneumonia group, and 100 healthy children who received vaccination in this hospital during the same period were selected as normal control group. The expression levels of P2X7 receptor, CD64 and CD54 as well as the contents of inflammatory factors, acute phase proteins and immunoglobulins in serum of the two groups were detected. Results: Immediately after admission, serum P2X7 receptor, CD64 and CD54 expression of bacterial pneumonia group were higher than those of normal control group, inflammatory cytokines TNF-α, sTREM-1, IL-2 and IL-6 contents were higher than those of normal control group, acute phase proteins 1-AGP, CRP, CP and HP contents were higher than those of normal control group, and immunoglobulins IgA, IgM and IgG contents were higher than those of normal control group;serum P2X7 receptor, CD64 and CD54 expression in children with bacterial pneumonia were positively correlated with TNF-α, sTREM-1, IL-2, IL-6, 1-AGP, CRP, CP, HP, IgA, IgM and IgG contents.Conclusion:The serum P2X7 receptor, CD64 and CD54 expression increase in children with bacterial pneumonia, and they are positively correlated with the degree of infection.展开更多
基金supported in part by the Science&Technology Commission of Shanghai Municipality(No.21S11906300 to Huili Lu,China)。
文摘Developing universal CARs with improved flexible targeting and controllable activities is urgently needed.While several studies have suggested the potential of CD16a in tandem with monoclonal antibodies to construct universal CAR-T cells,the weak affinity between them is one of the limiting factors for efficacy.Herein,we systematically investigated the impact of Fcγreceptor(FcγR)affinity on CAR-T cells properties by constructing universal CARs using Fcγreceptors with different affinities for IgG1 antibodies,namely CD16a,CD32a,and CD64.We demonstrated that the activities of these universal CAR-T cells on tumor cells could be redirected and regulated by IgG1 antibodies.In xenografted mice,64CAR chimeric Jurkat cells with the highest affinity showed significant antitumor effects in combination with herceptin in the HER2 low expression U251 MG model.However,in the CD20 high expression Raji model,64CAR caused excessive activation of CAR-T cells,which resulted in cytokine release syndrome(CRS)and the decline of antitumor activity,and 32CAR with a moderate affinity brought the best efficacy.Our work extended the knowledge about FcγR-based universal CAR-T cells and suggested that only the FcγRCAR with an appropriate affinity can offer the optimal antitumor advantages of CAR-T cells.
文摘Objective:To investigate the correlation of serum P2X7 receptor, CD64 and CD54 expression with infection process in children with bacterial pneumonia.Methods: A total of 164 children with bacterial pneumonia hospitalized in this hospital between June 2016 and February 2018 were selected as bacterial pneumonia group, and 100 healthy children who received vaccination in this hospital during the same period were selected as normal control group. The expression levels of P2X7 receptor, CD64 and CD54 as well as the contents of inflammatory factors, acute phase proteins and immunoglobulins in serum of the two groups were detected. Results: Immediately after admission, serum P2X7 receptor, CD64 and CD54 expression of bacterial pneumonia group were higher than those of normal control group, inflammatory cytokines TNF-α, sTREM-1, IL-2 and IL-6 contents were higher than those of normal control group, acute phase proteins 1-AGP, CRP, CP and HP contents were higher than those of normal control group, and immunoglobulins IgA, IgM and IgG contents were higher than those of normal control group;serum P2X7 receptor, CD64 and CD54 expression in children with bacterial pneumonia were positively correlated with TNF-α, sTREM-1, IL-2, IL-6, 1-AGP, CRP, CP, HP, IgA, IgM and IgG contents.Conclusion:The serum P2X7 receptor, CD64 and CD54 expression increase in children with bacterial pneumonia, and they are positively correlated with the degree of infection.
