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Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE).

接受嵌合抗原受体 T 细胞治疗的成人和儿童的管理: 欧洲血液和骨髓移植学会 (EBMT) 的最佳实践建议和 ISCT 和 EBMT 联合认证委员会 (JACIE)。

  • 影响因子:4.07
  • DOI:10.3324/haematol.2019.229781
  • 作者列表:"Yakoub-Agha I","Chabannon C","Bader P","Basak GW","Bonig H","Ciceri F","Corbacioglu S","Duarte RF","Einsele H","Hudecek M","Kersten MJ","Köhl U","Kuball J","Mielke S","Mohty M","Murray J","Nagler A","Robinson S","Saccardi R","Sanchez-Guijo F","Snowden JA","Srour M","Styczynski J","Urbano-Ispizua A","Hayden PJ","Kröger N
  • 发表时间:2020-01-31
Abstract

:Chimeric antigen receptor (CAR) T cells are a novel class of anti-cancer therapy in which autologous or allogeneic T cells are engineered to express a CAR targeting a membrane antigen. In Europe, tisagenlecleucel (Kymriah™) is approved for the treatment of refractory/relapsed acute lymphoblastic leukemia in children and young adults as well as relapsed/refractory diffuse large B-cell lymphoma, while axicabtagene ciloleucel (Yescarta™) is approved for the treatment of relapsed/refractory high-grade B-cell lymphoma and primary mediastinal B-cell lymphoma. Both agents are genetically engineered autologous T cells targeting CD19. These practical recommendations, prepared under the auspices of the European Society of Blood and Marrow Transplantation, relate to patient care and supply chain management under the following headings: patient eligibility, screening laboratory tests and imaging and work-up prior to leukapheresis, how to perform leukapheresis, bridging therapy, lymphodepleting conditioning, product receipt and thawing, infusion of CAR T cells, short-term complications including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, antibiotic prophylaxis, medium-term complications including cytopenias and B-cell aplasia, nursing and psychological support for patients, long-term follow-up, post-authorization safety surveillance, and regulatory issues. These recommendations are not prescriptive and are intended as guidance in the use of this novel therapeutic class.

摘要

: 嵌合抗原受体 (CAR) T 细胞是一类新型的抗癌治疗方法,其中自体或同种异体 T 细胞被改造以表达靶向膜抗原的 CAR。在欧洲,tisagenlecluel (Kymriah™) 被批准用于治疗儿童和年轻成人的难治性/复发性急性淋巴细胞白血病以及复发性/难治性弥漫性大 B 细胞淋巴瘤,而 axicabtagene ciloleucel (Yescarta™) 被批准用于治疗复发/难治性高级别 B 细胞淋巴瘤和原发性纵隔 B 细胞淋巴瘤。两种药物都是靶向 cd19 的基因工程自体 T 细胞。这些在欧洲血液和骨髓移植学会主持下编写的实用建议涉及以下标题下的患者护理和供应链管理: 患者资格, 筛查实验室检查和成像和检查在白细胞去除之前,如何进行白细胞去除,桥接治疗,淋巴消耗调理,产品接收和解冻,输注 CAR T 细胞,短期并发症包括细胞因子释放综合征和免疫效应细胞相关神经毒性综合征,抗生素预防, 中期并发症包括血细胞减少和 b细胞再生障碍性贫血,患者的护理和心理支持,长期随访,授权后安全性监测和监管问题。这些建议不是指令性的,旨在作为使用这种新型治疗类的指导。

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相关文献
影响因子:4.07
发表时间:2020-01-31
来源期刊:Haematologica
DOI:10.3324/haematol.2019.229781
作者列表:["Yakoub-Agha I","Chabannon C","Bader P","Basak GW","Bonig H","Ciceri F","Corbacioglu S","Duarte RF","Einsele H","Hudecek M","Kersten MJ","Köhl U","Kuball J","Mielke S","Mohty M","Murray J","Nagler A","Robinson S","Saccardi R","Sanchez-Guijo F","Snowden JA","Srour M","Styczynski J","Urbano-Ispizua A","Hayden PJ","Kröger N"]

METHODS::Chimeric antigen receptor (CAR) T cells are a novel class of anti-cancer therapy in which autologous or allogeneic T cells are engineered to express a CAR targeting a membrane antigen. In Europe, tisagenlecleucel (Kymriah™) is approved for the treatment of refractory/relapsed acute lymphoblastic leukemia in children and young adults as well as relapsed/refractory diffuse large B-cell lymphoma, while axicabtagene ciloleucel (Yescarta™) is approved for the treatment of relapsed/refractory high-grade B-cell lymphoma and primary mediastinal B-cell lymphoma. Both agents are genetically engineered autologous T cells targeting CD19. These practical recommendations, prepared under the auspices of the European Society of Blood and Marrow Transplantation, relate to patient care and supply chain management under the following headings: patient eligibility, screening laboratory tests and imaging and work-up prior to leukapheresis, how to perform leukapheresis, bridging therapy, lymphodepleting conditioning, product receipt and thawing, infusion of CAR T cells, short-term complications including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, antibiotic prophylaxis, medium-term complications including cytopenias and B-cell aplasia, nursing and psychological support for patients, long-term follow-up, post-authorization safety surveillance, and regulatory issues. These recommendations are not prescriptive and are intended as guidance in the use of this novel therapeutic class.

关键词: 暂无
翻译标题与摘要 下载文献
影响因子:3.07
发表时间:2020-02-01
来源期刊:Oncology reports
DOI:10.3892/or.2020.7457
作者列表:["Li C","Xu Y","Xin P","Zheng Y","Zhu X"]

METHODS:The aim of the present study was to explore the possible mechanisms of phosphatase and tensin homolog (PTEN) in the pathogenesis of Burkitt's lymphoma, and provide novel information that can be used in the targeted treatment of this disease. PTEN lentiviral overexpression vector and short‑hairpin PTEN silencing vectors were constructed. The effect of PTEN on the growth and proliferation of CA46 and RAJI cells was analyzed using a Cell Counting Kit‑8 assay. Apoptosis was detected by Hoechst 33342 and propidium iodide double staining. Flow cytometry was used to analyze the cell cycle. A Transwell chamber was used to detect cell migration and invasion abilities. Western blot analysis was used to detect related protein changes. The mechanism of the effect of PTEN on the biological characteristics of Burkitt's lymphoma cells was subsequently analyzed. The results revealed that PTEN inhibited the proliferation of CA46 and RAJI cells by downregulating the expression of p‑AKT, It was indicated that the upregulation of proapoptotic proteins (including Bad and Bax) induced apoptosis, regulated cyclin (including P53, P21, CDK4, CDK6, cyclin D3 and cyclin H) to inhibit cell cycle progression, and mediated epithelial‑mesenchymal transition‑like cell markers (including E‑cadherin, N‑cadherin, β‑catenin, TCF‑8, vimentin, Slug and Snail) to inhibit cell migration and invasion. In conclusion, the tumor‑suppressor gene PTEN inhibited the phosphoinositide 3‑kinase/protein kinase B (PI3K/AKT) signaling pathway and inhibited the proliferation and migration of Burkitt's lymphoma cells, induced apoptosis and cell cycle arrest, thus playing a crucial role in the pathogenesis of Burkitt's lymphoma.

关键词: 暂无
翻译标题与摘要 下载文献
影响因子:3.78
发表时间:2020-03-01
DOI:10.1016/j.biopha.2020.109811
作者列表:["Yan G","Lei H","He M","Gong R","Wang Y","He X","Li G","Pang P","Li X","Yu S","Du W","Yuan Y"]

METHODS:Melatonin (Mel) has been shown to involve in many essential cell functions via modulating many signaling pathways. We for the first time investigated that Mel exerted anti-tumor activities in Hodgkin lymphoma (HL) via inhibiting cell proliferation and promoting cell apoptosis. Further study revealed that Mel treatment increased expression of LC3-II and decreased p62 proteins with the enhanced production of autolysosome, indicating it induced activation of autophagy. Nevertheless, Mel treatment together with autophagy inhibitors 3-MA or CQ exacerbated the damage effect of Mel in HL cells, which means autophagy plays a protective role in this process. Furthermore, we found Mel treatment increased the expression of G protein-coupled receptors MT2 and retinoic acid-related orphan receptors (RORs), eg. RORA, RORB and RORC. While RORC has the highest increase in Mel treated HL cells. In addition, RORC overexpression induced autophagy activation. Therefore, Mel showed tumor-suppressive role due to an increased level of RORC induced autophagy in HL.

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