Anti-CD19 chimeric antigen receptor-modified T(CAR-T-19) cells have emerged as a powerful targeted immunotherapy for B-cell lineage acute lymphoblastic leukemia with a remarkable clinical response in recent trials. No...Anti-CD19 chimeric antigen receptor-modified T(CAR-T-19) cells have emerged as a powerful targeted immunotherapy for B-cell lineage acute lymphoblastic leukemia with a remarkable clinical response in recent trials. Nonetheless, few data are available on the subsequent clinical monitoring and treatment of the patients, especially those with disease recurrence after CAR-T-19 cell infusion. Here, we analyzed three patients who survived after our phase I clinical trial and who were studied by means of biomarkers reflecting persistence of CAR-T-19 cells in vivo and predictive factors directing further treatment. One patient achieved 9-week sustained complete remission and subsequently received an allogeneic hematopoietic stem cell transplant. Another patient who showed relapse after 20 weeks without detectable leukemia in the cerebrospinal fluid after CAR-T-19 cell treatment was able to achieve a morphological remission under the influence of stand-alone low-dose chemotherapeutic agents. The third patient gradually developed extensive extramedullary involvement in tissues with scarce immune-cell infiltration during a long period of hematopoietic remission after CAR-T-19 cell therapy. Long-term and discontinuous increases in serum cytokines(mainly interleukin 6 and C-reactive protein) were identified in two patients(Nos. 1 and 6) even though only a low copy number of CAR molecules could be detected in their peripheral blood. This finding was suggestive of persistent functional activity of CAR-T-19 cells. Combined analyses of laboratory biomarkers with their clinical manifestations before and after salvage treatment showed that the persistent immunosurveillance mediated by CAR-T-19 cells would inevitably potentiate the leukemia-killing effectiveness of subsequent chemotherapy in patients who showed relapse after CAR-T-19-induced remission.展开更多
Hierarchical hollow structure has demonstrated potential for enhancing electromagnetic(EM)attenuation and improving impedance matching,garnering significant attention for researching.Herein,we have successfully implem...Hierarchical hollow structure has demonstrated potential for enhancing electromagnetic(EM)attenuation and improving impedance matching,garnering significant attention for researching.Herein,we have successfully implemented compositional and structural engineering to fabricate hollow Mo2C/C microspheres with controllable composition by coupling interaction between dopamine hydrochloride and ammonium molybdate.With the synergistic effect of composition and hollow structure,the strongest reflection loss intensity and broadest effective absorption of the optimized sample reach-70.2 dB and 6.2 GHz,respectively.The formation of hollow heterogeneous structures not only favors impedance matching feature,but also generates considerable contribution to EM attenuation capacity.Furthermore,radar cross-section simulation data indicate that hollow Mo2C/C microspheres with compositional optimization and heterogeneous structures have broad prospects for practical applications.展开更多
基金supported by the National Science Foundation for Young Scientists of China (81402567, 81402566, 81472612)Bejing Nova Program (XX2016086)+3 种基金China Postdoctoral Science Foundation Grant (201150M1533)Science and Technology Planning Project of Beijing City (Z151100003915076 to Weidong Han)National Natural Science Foundation of China (31270820, 81230061 to Weidong Han)People’s Republic of China Support Fund (2015PC-TSYS-2013 to Suxia Li)
文摘Anti-CD19 chimeric antigen receptor-modified T(CAR-T-19) cells have emerged as a powerful targeted immunotherapy for B-cell lineage acute lymphoblastic leukemia with a remarkable clinical response in recent trials. Nonetheless, few data are available on the subsequent clinical monitoring and treatment of the patients, especially those with disease recurrence after CAR-T-19 cell infusion. Here, we analyzed three patients who survived after our phase I clinical trial and who were studied by means of biomarkers reflecting persistence of CAR-T-19 cells in vivo and predictive factors directing further treatment. One patient achieved 9-week sustained complete remission and subsequently received an allogeneic hematopoietic stem cell transplant. Another patient who showed relapse after 20 weeks without detectable leukemia in the cerebrospinal fluid after CAR-T-19 cell treatment was able to achieve a morphological remission under the influence of stand-alone low-dose chemotherapeutic agents. The third patient gradually developed extensive extramedullary involvement in tissues with scarce immune-cell infiltration during a long period of hematopoietic remission after CAR-T-19 cell therapy. Long-term and discontinuous increases in serum cytokines(mainly interleukin 6 and C-reactive protein) were identified in two patients(Nos. 1 and 6) even though only a low copy number of CAR molecules could be detected in their peripheral blood. This finding was suggestive of persistent functional activity of CAR-T-19 cells. Combined analyses of laboratory biomarkers with their clinical manifestations before and after salvage treatment showed that the persistent immunosurveillance mediated by CAR-T-19 cells would inevitably potentiate the leukemia-killing effectiveness of subsequent chemotherapy in patients who showed relapse after CAR-T-19-induced remission.
基金supported by the National University of Defense Technology Independent Innovation Science Fund(No.24-ZZCXJDZ-42)the Postdoctoral Fellowship Program of CPSF(No.GZC20241747).
文摘Hierarchical hollow structure has demonstrated potential for enhancing electromagnetic(EM)attenuation and improving impedance matching,garnering significant attention for researching.Herein,we have successfully implemented compositional and structural engineering to fabricate hollow Mo2C/C microspheres with controllable composition by coupling interaction between dopamine hydrochloride and ammonium molybdate.With the synergistic effect of composition and hollow structure,the strongest reflection loss intensity and broadest effective absorption of the optimized sample reach-70.2 dB and 6.2 GHz,respectively.The formation of hollow heterogeneous structures not only favors impedance matching feature,but also generates considerable contribution to EM attenuation capacity.Furthermore,radar cross-section simulation data indicate that hollow Mo2C/C microspheres with compositional optimization and heterogeneous structures have broad prospects for practical applications.
