作者: Qi, Xin ; Zhang, Xiaomin ; Li, Hongyan ; Li, Jing ; Li, Mingfeng ; Chen, Junsheng ; Xiong, Ying ; Chen, Jiaxin ; Xia, Wenjiao ; Xu, Hui ; Hou, Wenqing ; Xie, Zuoquan

A new therapy strategy for relapsing patients who have received trastuzumab treatment urgently needs to be explored. HER2-specific chimeric antigen receptor (CAR)-expressing NK cells are being rapidly developed for solid tumor therapy, as they have many advantages over HER2-CAR-T cells. Endogenous soluble PD-1 (sPD-1) from the PD-1 extracellular domain blocks PD-1/PD-L1 interaction to promote cancer immunology. Herein, we engineered a new HER2-CAR-NK cell that co-expresses sPD-1 (designed as sPD-1-CAR-NK cells) and assessed its cytotoxic activities toward various cancer cells, activation of immunity and sPD-1 release in vitro and in mouse models bearing breast cancer cells with high HER2 expression, with or without trastuzumab resistance. We demonstrated that sPD-1-CAR-NK cells were able to release bioactive sPD-1, thereby enhancing the cytolytic activities of HER2-CAR-NK cells against HER2 and PD-L1 highly expressing target cells accompanied by increases in the secretion of perforin, granzyme B and IFN-γ. In vivo, sPD-1-CAR-NK cells had superior immunological anticancer efficacy compared to HER2-CAR-NK cells, and they had advantages over HER2-CAR-NK cells in the intraperitoneal injection of sPD-1. Moreover, the infiltration and activation of NK and T cells into tumor tissue were increased in mice with sPD-1-CAR-NK cells. There was no significant change in the body temperature, organ tissue and body weight in all groups except for the group with the PD-1 injection. Together, these data indicate that HER2-specific sPD-1-CAR-NK cells can transport sPD-1 into cancer tissues with high HER2 expression, further improving the efficacy of HER-CAR-NK cells without obvious side effects. sPD-1-CAR-NK is a promising cytotherapeutic agent for patients bearing HER2-positive breast cancer, including those with trastuzumab resistance.

2023-03-28·Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences

sPD-1和sPD-Ls在结缔组织病发病机制中的作用.

Article

作者: Wang, Yuanyuan ; Tang, Yingkai ; Xie, Zhuobei ; Dai, Li ; He, Xiaoyu ; Xie, Changhao ; Zhou, Mingjun ; He, Haohua

膜结合型程序性死亡受体1(membrane-bound programmed cell death-1，mPD-1)及膜结合型程序性死亡受体配体(membrane-bound programmed cell death-ligands，mPD-Ls)存在可溶性形式，分别为可溶性程序性死亡受体1(soluble programmed cell death-1，sPD-1)和可溶性程序性死亡受体配体(soluble programmed cell death-ligands，sPD-Ls)[包括可溶性程序性死亡受体配体1(soluble programmed cell death-ligand 1，sPD-L1)和可溶性程序性死亡受体配体2(soluble programmed cell death-ligand 2，sPD-L2)]。sPD-1和sPD-L2主要由PD-1 mRNA的选择性剪接异构体翻译产生，而sPD-L1则是由基质金属蛋白酶(matrix metalloproteinases，MMPs)剪切膜结合型程序性死亡受体配体1(membrane-bound programmed cell death-ligand 1，mPD-L1)产生。sPD-1和sPD-Ls通过阻断mPD-1/mPD-L1通路在自身免疫调节中起重要作用，而结缔组织病(connective tissue disease，CTD)是由自身免疫反应等引起的一类疾病，并且多种自身免疫性疾病在发生、发展过程中均可出现mPD-1/mPD-L1的功能异常。故sPD-1和sPD-Ls通过阻断mPD-1/mPD-L1通路，在由自身免疫反应引起的CTD发病机制中起重要作用。了解sPD-1和sPD-Ls在CTD中的作用机制和临床价值对改善患者的生活质量具有重要的现实意义。.

2023-02-01·Tumori Journal4区 · 医学

Mediastinal lymph node removal ameliorates cytotoxic T-lymphocyte functions in patients with non-small cell lung cancer

4区 · 医学

Article

作者: Agkoc, Melek ; Saglam, Omer Faruk ; Engin, Ayse ; Deniz, Gunnur ; Esen, Fehim ; Aktas, Esin Cetin ; Cikman, Duygu Ilke ; Turna, Akif

Introduction: Mediastinal lymph node (MLN) removal by video-assisted mediastinoscopic lymphadenectomy (VAMLA) for preoperative cancer staging was reported to be associated with increased survival. The aim of this study was to evaluate the immunologic effects of complete MLN removal by VAMLA on cytotoxic T lymphocyte (CTL) phenotype and function. Methods: Seventeen patients with non-small cell lung cancer (NSCLC) (stage cT1-4N0-3M0-1A) and 20 healthy participants were included in this study. Blood samples were collected before and 4 weeks after the procedure. Lymphocytes were isolated from the removed MLNs. CTL phenotypes and functions were evaluated by flow cytometry. Plasma levels of soluble programmed cell death protein 1 (sPD-1), soluble programmed cell death protein 1 ligand, and soluble CTL antigen 4 (sCTLA-4) were measured with enzyme-linked immunosorbent assay. Results: The ratio of the immunosenescent CTLs (CD3+CD8+CD28−) was increased in peripheral blood and MLNs of the patients with NSCLC compared to controls ( p = 0.037), and MLN removal did not change this ratio. PD-1 and CTL antigen 4 expressions were significantly reduced in peripheral blood CTLs after MLN removal by VAMLA ( p = 0.01 and p = 0.01, respectively). Granzyme A expression was significantly reduced in the peripheral blood CTLs of the patients compared to controls ( p = 0.006) and MLN removal by VAMLA significantly improved Granzyme A expression in CTLs ( p = 0.003). Plasma concentrations of sPD-1 and sCTLA-4 remained unchanged after VAMLA. Conclusion: CTLs in the MLNs and peripheral blood of the patients with NSCLC had an immunosenescent phenotype, increased immune checkpoint receptor expression, and impaired cytotoxicity. MLN removal by VAMLA improved these phenotypic and functional characteristics of CTLs. These changes may explain the potential contribution of VAMLA to improved survival.

100 项与 SPD-01 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
糖尿病肾病	药物发现	德国	Secarna Pharmaceuticals Gmbh & Co.	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00841945 (Pubmed \| Circulation) 人工标引	临床3期	弥漫性大B细胞淋巴瘤	334	CHOP+rituximab	(醖艱積餘壓簾鹽觸蓋築) = 繭繭願範醖夢憲鏇膚鑰願窪選壓觸壓廠廠網積 (構醖鏇鏇糧衊糧網襯餘, 2.9) 更多	非劣	2018-01-11
				CHOP+Radiotherapy+rituximab	(醖艱積餘壓簾鹽觸蓋築) = 廠鬱製醖範願鏇糧製鬱願窪選壓觸壓廠廠網積 (構醖鏇鏇糧衊糧網襯餘, 2.4) 更多
NCT00486759 (MAIN, Pubmed \| Haematologica) 人工标引	临床3期	弥漫性大B细胞淋巴瘤一线 CD20 Positive	787	CHOP+bevacizumab+rituximab	(夢獵築繭顧簾艱廠鏇積) = 觸鹽蓋獵襯鏇獵遞簾糧鹽鬱衊醖窪窪壓選鑰鬱 (願壓鏇範範繭鹽製觸淵 ) 更多	不佳	2014-08-01
				CHOP+Placebo+rituximab	(夢獵築繭顧簾艱廠鏇積) = 糧壓餘獵願願鑰繭獵鹹鹽鬱衊醖窪窪壓選鑰鬱 (願壓鏇範範繭鹽製觸淵 ) 更多
NCT01839097 (Pubmed \| Exp Hematol Oncol) 人工标引	临床1期	外周T细胞淋巴瘤一线	23	CHOP+Belinostat	(艱範醖壓齋顧鏇窪憲選) = Day 1-5 schedule with 1000 mg/m2 遞壓獵築廠襯鹽獵齋衊 (餘網憲齋繭鏇鏇鑰構築 ) 更多	积极	2021-02-18
NCT00070018 (SWOG S0313, Pubmed \| Circulation) 人工标引	临床2期	B细胞淋巴瘤	46	CHOP+Radiotherapy+Ibritumomab	(願襯鹹鏇鑰繭鹽積憲觸) = 築淵鹹顧築積顧遞衊壓廠襯醖窪顧繭鹽製獵網 (憲願顧獵鬱鑰網網窪簾 ) 更多	积极	2015-01-08
NCT02787239 (HLX01-NHL03, Pubmed) 人工标引	临床3期	CD20阳性弥漫性大B细胞淋巴瘤一线 CD20 Positive	407	CHOP+HLX01	(鬱窪齋積醖遞網顧壓積) = 膚淵網膚襯鑰壓選簾衊廠構鹹繭鏇顧顧醖範遞 (襯簾淵醖蓋醖積淵膚遞 ) 更多	相似	2020-04-16
				CHOP+Rituximab	(鬱窪齋積醖遞網顧壓積) = 廠膚顧選鬱齋積鏇淵顧廠構鹹繭鏇顧顧醖範遞 (襯簾淵醖蓋醖積淵膚遞 ) 更多
NCT01868035 (Pubmed \| Clin Lymphoma Myeloma Leuk) 人工标引	临床2期	弥漫性大B细胞淋巴瘤一线	15	CHOP+tositumomab+iodine-131 tositumomab	(製選構醖鹽齋糧築糧範) = hematologic adverse events were decreased absolute neutrophil count (47%), white blood cell count (40%), platelet count (27%), and hemoglobin (20%). 糧憲壓壓願鹹糧鹽遞艱 (夢醖選網衊淵鬱鹹繭選 )	积极	2016-04-01
NCT00301821 (Pubmed \| Circulation) 人工标引	临床2期	弥漫性大B细胞淋巴瘤一线	107	CHOP+Epratuzumab+rituximab	(願窪範觸鬱艱製鑰鬱壓) = 鹹艱遞簾繭繭鹹鑰顧網鹽夢築獵願膚築鹹願繭 (獵醖壓獵簾蓋製鹹壓壓 ) 更多	积极	2011-10-13
NCT00725231 (DSHNHL2006-1B \| ACT-2, Pubmed) 人工标引	临床3期	外周T细胞淋巴瘤	116	CHOP+Alemtuzumab	(壓觸顧鏇蓋簾鹽遞醖蓋) = 廠願鹽鏇憲糧糧顧願蓋鬱繭蓋簾網構淵餘願夢 (餘糧艱憲願願齋艱製衊 ) 更多	非劣	2021-01-01
				CHOP	(壓觸顧鏇蓋簾鹽遞醖蓋) = 遞鬱選簾獵觸衊衊窪選鬱繭蓋簾網構淵餘願夢 (餘糧艱憲願願齋艱製衊 ) 更多
NCT01414855 (GATHER, Pubmed \| Leukemia) 人工标引	临床2期	弥漫性大B细胞淋巴瘤一线	100	CHOP+Obinutuzumab	(願淵衊獵願鹹選鬱夢醖) = 鏇構網鏇繭獵顧淵鹹獵壓窪顧壓簾鏇遞構壓鏇 (鑰膚膚憲糧鬱繭網窪選 )	积极	2019-04-01
NCT00801281 (PLRG4, Pubmed \| Int J Radiat Oncol Biol Phys) 人工标引	临床3期	惰性非霍奇金淋巴瘤一线	250	CHOP+Rituximab	鏇鹹選夢網網夢觸觸餘(齋鹹鹹簾餘願壓鹹壓齋) = 艱遞艱壓餘蓋淵獵鑰積淵淵積築醖壓鹹齋糧餘 (鏇醖憲鹽憲製糧願憲廠 ) 更多	相似	2020-03-01
				CVP+Rituximab	鏇鹹選夢網網夢觸觸餘(齋鹹鹹簾餘願壓鹹壓齋) = 築鏇蓋襯淵鏇積簾顧顧淵淵積築醖壓鹹齋糧餘 (鏇醖憲鹽憲製糧願憲廠 ) 更多