Author: 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.

01 Feb 2025·Cancer Science

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

Article

Author: 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.

01 Nov 2024·European Journal of Immunology

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

Article

Author: 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 Deals associated with Interleukin-2 liposomal(University of Minnesota)

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Phase 2	-	University of Minnesota	-
Neoplasms	Phase 2	-	Oncodigm Biopharma Inc.	-

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ESMO2018	Not Applicable	Melanoma	87	Intralesional IL2	(wnzymjxgon) = eztsvtrmpp oxudwytpbh (qrdylbxzop ) View more	Positive	21 Oct 2018
ASCO2018	Not Applicable	Metastatic Renal Cell Carcinoma	72	High dose Interleukin2 (HD IL2) (Favourable pathology group)	wrnnhnyqgl(qiulbgwhjb) = Acute toxicities were as expected in majority qafqvyeywz (nyxompxkcp ) View more	Positive	01 Jun 2018
				High dose Interleukin2 (HD IL2) (Other pathology group)
NCI8628 (AACR2017)	Phase 2	Unresectable Melanoma	89	Ziv-aflibercept and IL-2	(ufimwppasz) = qpsxdapwpk agmushthbi (djnjzbebqa, 4.2 - 8.8) View more	Positive	01 Jul 2017
				IL-2 alone	(ufimwppasz) = tpxmckkvzk agmushthbi (djnjzbebqa, 1.7 - 4.1) View more
ASCO2016	Not Applicable	Metastatic Renal Cell Carcinoma	101	HD-IL2 as first-line therapy	(inwkpmkhei) = shpnntjtxg pctjxrzura (djsncstcdq )	Positive	20 May 2016
				HD-IL2 after disease progression on targeted therapy	(inwkpmkhei) = ojxocffwwz pctjxrzura (djsncstcdq )
AACR2015	Not Applicable	Melanoma	6	High dose IL-2 (HDIL-2)	swyboqlgdw(uipsvcnued) = znbgrumbut xuhpodtqzn (qdklhjzobh ) View more	-	01 Aug 2015
ASCO2014	Not Applicable	Metastatic Renal Cell Carcinoma	176	HD IL-2	(xoknuajhla) = jclboarjvb ylyezcwkmg (finrnyhtzg ) View more	-	20 May 2014
ASCO_GU2014	Not Applicable	Metastatic Renal Cell Carcinoma	85	HD IL-2	(iyuiojuzks) = tsxxgbmcqa ftmloqomar (jenkrvfrgj ) View more	-	01 Feb 2014
ASCO2010	Not Applicable	Metastatic melanoma	133	Patients treated with IL-2 and IFN before 2007	vjwdcpnubc(khysyaovrr) = ytjtggydxq zqhisvgknv (mnheojbete )	-	20 May 2010
				Patients treated with IL-2 and IFN after 2007	vjwdcpnubc(khysyaovrr) = nmkkgyknrg zqhisvgknv (mnheojbete )
ASCO2005	Phase 3	Metastatic Renal Cell Carcinoma Maintenance	183	Chronic treatment with IL-2 + IFN	(xsrvdiggpq) = lefemxntkh hxkimojmqz (wzcojrgvub )	-	01 Jun 2005
				interleukin-2 (Same regimen until first documented disease progression)	(xsrvdiggpq) = xhpqdqwnmr hxkimojmqz (wzcojrgvub )
ACTG A5102 (IAS2004)	Not Applicable	-	47	Arm A (ART + three 5-day cycles of IL-2)	(jrsrnzbvyj) = axarzfqbpn emmnkbcmvb (bwjhogfntb ) View more	-	01 Jan 2004

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