作者: Klufas, Daniel M. ; Leboit, Phoebe E. ; Moss, Madison I. ; Patel, Dhara U. ; Neuhaus, Isaac M. ; Kyle, Ryan L. ; Kim, Esther A. ; Yates, Ashley E. ; Cohen, Jarish N. ; Kelly, Matthew ; Rosenblum, Michael D. ; Harris, Hobart W. ; Lowe, Margaret M. ; Hansen, Scott L. ; Naik, Haley B.

ABSTRACTHidradenitis suppurativa (HS) is a relatively common and highly morbid inflammatory skin disease. Due to the relatively limited understanding of HS's pathogenesis, there are currently insufficient treatment options available, and many patients' medical needs are not being met. This is partly due to the historical scarcity of ex vivo assays and animal models that accurately recapitulate the disease. Thus, we have developed a standardised whole‐tissue explant model of HS to examine its pathogenic mechanisms and the efficacy of potential treatments within intact human tissue. We measured cytokine protein and RNA within whole tissue maintained in an agar‐media solution, finding that IL‐6 and IL‐8 concentrations trended upwards in both HS explants and healthy controls, while IL‐17A, IL‐1β, and TNF‐α exhibited increases in HS tissue alone. We also show that the explants were responsive to treatment with both dexamethasone and IL‐2. Not only do our results show that this model effectively delivers treatments throughout the explants, but they also elucidate which cytokines are related to the explant process regardless of tissue state and which are related to HS tissue specifically, laying the groundwork for future implementations of this model.

2025-02-01·Cancer Science

Elotuzumab‐mediated ADCC with Th1‐like Vγ9Vδ2 T cells to disrupt myeloma–osteoclast interaction

Article

作者: Miki, Hirokazu ; Sumitani, Ryohei ; Maruhashi, Tomoko ; Oura, Masahiro ; Kagawa, Kumiko ; Abe, Masahiro ; Teramachi, Jumpei ; Maeda, Yusaku ; Takahashi, Mamiko ; Oda, Asuka ; Fujii, Shiro ; Tenshin, Hirofumi ; Inoue, Yusuke ; Nakamura, Shingen ; Endo, Itsuro ; Hara, Tomoyo ; Hiasa, Masahiro ; Sogabe, Kimiko ; Harada, Takeshi ; Ozaki, Shuji

AbstractMultiple myeloma (MM) cells and osteoclasts (OCs) activate with each other to cause drug resistance. Human Th1‐like Vγ9Vδ2 (γδ) T cells, important effectors against tumors, can be expanded and activated ex vivo by the aminobisphosphonate zoledronic acid in combination with IL‐2. We previously reported that the expanded γδ T cells effectively targeted and killed OCs as well as MM cells. Because the expanded γδ T cells expressed CD16 on their surface, we investigated the utilization of the expanded γδ T cells for antibody‐dependent cellular cytotoxicity (ADCC). Although the expanded γδ T cells alone induced cell death in MM cell lines, the addition of the anti‐SLAMF7 monoclonal antibody elotuzumab (ELO) further enhanced their cytotoxic activity only against SLAMF7‐expressing MM cell lines and primary MM cells. Intriguingly, ELO was also able to enhance γδ T cell‐induced cell death against OCs cultured alone, and against both MM cells and OCs in their coculture settings. SLAMF7 was found to be highly expressed in OCs differentiated in vitro from monocytes by receptor activator of nuclear factor‐κ B ligand and M‐CSF, although monocytes only marginally expressed SLAMF7. These results demonstrate that SLAMF7 is highly expressed in both MM cells and OCs, and that the ex vivo‐expanded γδ T cells can exert ELO‐mediated ADCC against SLAMF7‐expressing MM cells and OCs besides their direct cytotoxic activity. Further study is warranted for the innovative utilization of γδ T cells.

2024-11-01·European Journal of Immunology

In vitro modulation of T cells in myasthenia gravis by low‐dose IL‐2

Article

作者: Durmuş, Hacer ; Akan, Onur ; Parman, Yeşim ; Aysal, Fikret ; Çebi, Merve ; Çakar, Arman ; Saruhan‐Direskeneli, Güher

AbstractFollicular helper (Tfh), peripheral helper (Tph), and regulatory (Treg) T cells are involved in myasthenia gravis (MG) pathogenesis, an autoimmune disorder arising from autoantibodies targeting neuromuscular junction proteins. This study explores the impact of low‐dose IL‐2 on Tfh, Tph, and Treg cells in vitro in MG. Acetylcholine‐receptor antibody‐positive MG (AChR‐MG), muscle‐specific kinase antibody‐positive MG (MuSK‐MG) patients, and healthy controls (HC) were studied. Blood cells were cultured with/without IL‐2 and compared by the ratios of IL‐2 stimulated/unstimulated cultures. In both AChR‐MG and MuSK‐MG patients, CD25+FoxP3+Tregs were lower, while CXCR5+PD‐1+ or ICOS+Tfh and CXCR5−PD‐1+ or ICOS+Tph cells were higher compared with HC. Among the MG group, the FoxP3+ Treg cells in AChR‐MG patients were even lower compared with MuSK‐MG patients. In vitro IL‐2 stimulation increased Tregs in all groups while decreasing PD‐1+/ICOS+Tfh and PD‐1+/ICOS+Tph populations. The fold‐increase ratio of Tregs and the fold‐decrease ratio of PD‐1+ or ICOS+Tfh and ICOS+Tph cells in AChR‐MG and MuSK‐MG patients were greater than in HCs. Low‐dose IL‐2 treatment may balance Tfh, Tph, and Treg cells in MG patients, offering a potential opportunity for disease modulation.

100 项与 Interleukin-2 liposomal(University of Minnesota) 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
肿瘤	临床2期	-	University of Minnesota	-
肿瘤	临床2期	-	Oncodigm Biopharma Inc.	-

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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


ESMO2018	N/A	黑色素瘤	87	Intralesional IL2	(獵艱鑰膚獵觸襯鬱艱顧) = 觸遞簾簾繭夢鏇鑰齋餘願構醖艱蓋築構夢顧鏇 (網醖膚膚糧構壓選顧願 ) 更多	积极	2018-10-21
ASCO2018	N/A	转移性肾细胞癌	72	High dose Interleukin2 (HD IL2) (Favourable pathology group)	鑰膚衊壓鏇積繭願鏇鬱(構簾醖範淵選鏇衊簾鏇) = Acute toxicities were as expected in majority 選憲鏇襯夢齋選蓋淵網 (鏇膚鹽簾襯遞憲遞獵鹽 ) 更多	积极	2018-06-01
				High dose Interleukin2 (HD IL2) (Other pathology group)
NCI8628 (AACR2017)	临床2期	不可切除的黑色素瘤	89	Ziv-aflibercept and IL-2	(網築積繭夢鬱鹹齋膚願) = 願顧壓鏇構醖繭選鹽繭廠鏇鏇衊獵鹽遞繭積顧 (襯夢衊蓋構遞壓鑰淵淵, 4.2 ~ 8.8) 更多	积极	2017-07-01
				IL-2 alone	(網築積繭夢鬱鹹齋膚願) = 膚範製齋繭餘鬱糧遞鹽廠鏇鏇衊獵鹽遞繭積顧 (襯夢衊蓋構遞壓鑰淵淵, 1.7 ~ 4.1) 更多
ASCO2016	N/A	转移性肾细胞癌	101	HD-IL2 as first-line therapy	(窪選觸網鹽製襯鹹醖鏇) = 築願糧鑰願網艱衊選積築淵衊繭衊願築範網醖 (淵蓋鏇簾觸鏇餘膚衊鏇 )	积极	2016-05-20
				HD-IL2 after disease progression on targeted therapy	(窪選觸網鹽製襯鹹醖鏇) = 鏇鬱艱夢積繭繭構遞醖築淵衊繭衊願築範網醖 (淵蓋鏇簾觸鏇餘膚衊鏇 )
AACR2015	N/A	黑色素瘤	6	High dose IL-2 (HDIL-2)	繭繭壓夢廠蓋壓顧窪繭(鑰願顧廠糧顧鬱窪餘繭) = 簾淵憲構艱壓構廠鏇選廠選齋膚廠鬱鹹積製簾 (夢顧鹹齋夢醖積範鏇窪 ) 更多	-	2015-08-01
ASCO2014	N/A	转移性肾细胞癌	176	HD IL-2	(鹽顧築夢夢遞窪簾願衊) = 夢遞選衊襯鹽醖艱遞夢網糧醖醖廠糧鬱窪選鑰 (糧簾築鬱網築鬱鹹積淵 ) 更多	-	2014-05-20
ASCO_GU2014	N/A	转移性肾细胞癌	85	HD IL-2	(選製網糧衊築網憲範蓋) = 願艱製襯範獵遞襯鏇窪壓獵膚鹽築醖夢顧糧構 (壓糧製淵獵範窪網顧鑰 ) 更多	-	2014-02-01
ASCO2010	N/A	转移性黑色素瘤	133	Patients treated with IL-2 and IFN before 2007	願窪鏇積鏇願鏇鹹襯夢(醖鑰憲衊糧艱艱醖選衊) = 網構憲廠積築網構遞餘積願繭廠願簾顧鏇鹽餘 (艱艱壓廠構簾鑰構選齋 )	-	2010-05-20
				Patients treated with IL-2 and IFN after 2007	願窪鏇積鏇願鏇鹹襯夢(醖鑰憲衊糧艱艱醖選衊) = 憲築憲餘鏇齋壓鹹膚製積願繭廠願簾顧鏇鹽餘 (艱艱壓廠構簾鑰構選齋 )
ASCO2005	临床3期	转移性肾细胞癌维持	183	Chronic treatment with IL-2 + IFN	(選築鏇簾夢衊鑰艱蓋淵) = 膚襯襯蓋憲蓋醖憲鑰淵鏇鏇襯簾醖夢範鬱築積 (鏇構壓獵憲選餘醖壓顧 )	-	2005-06-01
				interleukin-2 (Same regimen until first documented disease progression)	(選築鏇簾夢衊鑰艱蓋淵) = 襯觸憲襯鬱廠糧艱鑰蓋鏇鏇襯簾醖夢範鬱築積 (鏇構壓獵憲選餘醖壓顧 )
ACTG A5102 (IAS2004)	N/A	-	47	Arm A (ART + three 5-day cycles of IL-2)	(鹽餘醖網簾艱醖網衊糧) = 壓廠繭觸艱簾壓醖積製鹹鏇廠膚鏇築糧選構網 (遞廠廠繭觸醖壓廠築窪 ) 更多	-	2004-01-01