目的探讨白细胞分化抗原38(Cluster of Differentiation 38,CD38)、白细胞分化抗原138(Cluster of Differentiation 138,CD138)联合宫腔镜诊断反复胚胎移植失败(Repeated Implantation Failure,RIF)病人罹患慢性子宫内膜炎(Chronic Endo...目的探讨白细胞分化抗原38(Cluster of Differentiation 38,CD38)、白细胞分化抗原138(Cluster of Differentiation 138,CD138)联合宫腔镜诊断反复胚胎移植失败(Repeated Implantation Failure,RIF)病人罹患慢性子宫内膜炎(Chronic Endometri⁃tis,CE)的临床价值。方法对中国科学技术大学附属第一医院2017年2月至2019年6月186例RIF病人行宫腔镜检查,获取组织标本后行CD38、CD138免疫组化染色,计算分析CE患病率及宫腔镜检查诊断的灵敏度、特异度、阳性预测值、阴性预测值等指标。结果41.40%的RIF病人诊断出组织病理学CE,宫腔镜对CE检查结果与组织病理学结果具有中度一致性(Kappa=0.553),灵敏度为94.81%,特异度为64.22%,阳性预测值为65.18%,阴性预测值为94.60%。结论在RIF病人中,采用CD38、CD138免疫组化技术联合宫腔镜检查诊断CE,可提高诊断的准确率,为CE病人的系统性治疗提供指导,值得推广。展开更多
Chimeric antigen receptor T-cell(CAR T) therapy is a kind of effective cancer immunotherapy. However,designing CARs remains a challenge because many targetable antigens are shared by T cells and tumor cells. This shar...Chimeric antigen receptor T-cell(CAR T) therapy is a kind of effective cancer immunotherapy. However,designing CARs remains a challenge because many targetable antigens are shared by T cells and tumor cells. This shared expression of antigens can cause CAR T cell fratricide. CD38-targeting approaches(e.g.,daratumumab) have been used in clinical therapy and have shown promising results. CD38 is a kind of surface glycoprotein present in a variety of cells, such as T lymphocytes and tumor cells. It was previously reported that CD38-based CAR T cells may undergo apoptosis or T cell-mediated killing(fratricide) during cell manufacturing. In this study, a CAR containing a sequence targeting human CD38 was designed to be functional. To avoid fratricide driven by CD38 and ensure the production of CAR T cells, two distinct strategies based on antibodies(clone MM12 T or clone MM27) or proteins(H02 H or H08 H) were used to block CD38 or the CAR single-chain variable fragment(scFv) domain, respectively, on the T cell surface.The results indicated that the antibodies or proteins, especially the antibody MM27, could affect CAR T cells by inhibiting fratricide while promoting expansion and enrichment. Anti-CD38 CAR T cells exhibited robust and specific cytotoxicity to CD38+ cell lines and tumor cells. Furthermore, the levels of the proinflammatory factors TNF-a, IFN-g and IL-2 were significantly upregulated in the supernatants of A549CD38+ cells. Finally, significant control of disease progression was demonstrated in xenograft mouse models. In conclusion, these findings will help to further enhance the expansion, persistence and function of anti-CD38 CAR T cells in subsequent clinical trials.展开更多
文摘目的探讨白细胞分化抗原38(Cluster of Differentiation 38,CD38)、白细胞分化抗原138(Cluster of Differentiation 138,CD138)联合宫腔镜诊断反复胚胎移植失败(Repeated Implantation Failure,RIF)病人罹患慢性子宫内膜炎(Chronic Endometri⁃tis,CE)的临床价值。方法对中国科学技术大学附属第一医院2017年2月至2019年6月186例RIF病人行宫腔镜检查,获取组织标本后行CD38、CD138免疫组化染色,计算分析CE患病率及宫腔镜检查诊断的灵敏度、特异度、阳性预测值、阴性预测值等指标。结果41.40%的RIF病人诊断出组织病理学CE,宫腔镜对CE检查结果与组织病理学结果具有中度一致性(Kappa=0.553),灵敏度为94.81%,特异度为64.22%,阳性预测值为65.18%,阴性预测值为94.60%。结论在RIF病人中,采用CD38、CD138免疫组化技术联合宫腔镜检查诊断CE,可提高诊断的准确率,为CE病人的系统性治疗提供指导,值得推广。
基金supported by the grants from the National Natural Science Foundation of China (Nos. 81830002 and 31870873 to W.D.H.)the National Key Research and Development Program of China (Nos. 2016YFC1303501 and 2016YFC1303504 to WDH, and No. 2017YFC0909803 to W.Y.)
文摘Chimeric antigen receptor T-cell(CAR T) therapy is a kind of effective cancer immunotherapy. However,designing CARs remains a challenge because many targetable antigens are shared by T cells and tumor cells. This shared expression of antigens can cause CAR T cell fratricide. CD38-targeting approaches(e.g.,daratumumab) have been used in clinical therapy and have shown promising results. CD38 is a kind of surface glycoprotein present in a variety of cells, such as T lymphocytes and tumor cells. It was previously reported that CD38-based CAR T cells may undergo apoptosis or T cell-mediated killing(fratricide) during cell manufacturing. In this study, a CAR containing a sequence targeting human CD38 was designed to be functional. To avoid fratricide driven by CD38 and ensure the production of CAR T cells, two distinct strategies based on antibodies(clone MM12 T or clone MM27) or proteins(H02 H or H08 H) were used to block CD38 or the CAR single-chain variable fragment(scFv) domain, respectively, on the T cell surface.The results indicated that the antibodies or proteins, especially the antibody MM27, could affect CAR T cells by inhibiting fratricide while promoting expansion and enrichment. Anti-CD38 CAR T cells exhibited robust and specific cytotoxicity to CD38+ cell lines and tumor cells. Furthermore, the levels of the proinflammatory factors TNF-a, IFN-g and IL-2 were significantly upregulated in the supernatants of A549CD38+ cells. Finally, significant control of disease progression was demonstrated in xenograft mouse models. In conclusion, these findings will help to further enhance the expansion, persistence and function of anti-CD38 CAR T cells in subsequent clinical trials.
