Novel Antigens Targeted by ex Vivo Expanded T-Lymphocytes for Prevention or Treatment of Viral Infections Following Hematopoietic Stem Cell Transplantation

This Phase I dose-escalation trial is designed to evaluate the safety of rapidly generated multivirus-specific T-cell products with antiviral activity against CMV, EBV, adenovirus, HHV6, BK virus, JC virus, and human parainfluenza-3 (HPIV3), derived from eligible HSCT donors.
In this trial, we will utilize a rapid generation protocol for broad spectrum multivirus-specific T cells for infusion to recipients of allogeneic hematopoietic stem cell transplant (HSCT), who are at risk of developing EBV, CMV, adenovirus, HHV6, BKV, JCV and/or HPIV3, or with PCR/culture confirmed active infection(s) of EBV, CMV, adenovirus, HHV6, BKV, JCV, and/or HPIV3 that has failed to resolve with at least 14 days of standard antiviral therapy (if available and tolerated). These cells will be derived from HSCT donors, and the study agent will be assessed at each dose for evidence of dose-limiting toxicities (DLT).
This study will have two arms: Arm A will include patients who receive prophylactic treatment, and Arm B will include patients who receive VSTs for one or more active infections with targeted viruses. Determination of the study arm will be determined by the patient's clinical status. Study arms will each be analyzed for safety endpoints and secondary endpoints.

开始日期2017-02-15

申办/合作机构

Children's National Research Institute

100 项与 Viral specific VST(Children's National Research Institute) 相关的临床结果

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100 项与 Viral specific VST(Children's National Research Institute) 相关的转化医学

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100 项与 Viral specific VST(Children's National Research Institute) 相关的专利（医药）

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项与 Viral specific VST(Children's National Research Institute) 相关的文献（医药）

2024-12-01·Journal of Controlled Release

Surface-engineered mesenchymal stem cell for refractory asthma therapy: Reversing airway remodeling

Article

作者: Wang, Jing ; Han, Meng-Meng ; He, Xing-Yue ; Jeong, Jee-Heon ; Wei, Ning ; Wang, Yi ; Xing, Lei ; Zhou, Fang ; Tang, Ling ; Zhao, Yu-Chen ; Jiang, Hu-Lin ; Wang, Guang-Ji

In the development of asthma, subepithelial fibrosis and vascular proliferation cause airway remodeling and narrowing, leading to disease deterioration and respiratory failure. In the clinic, the treatment of asthma was aimed at reducing the frequency of acute asthma attacks through inhaled corticosteroids (ICSs). However, ICSs cannot prevent the progression into refractory asthma due to the formation of airway remodeling mainly by subepithelial fibrosis and angiogenesis surrounding the tracheal lumen. Herein, we constructed surface-engineered mesenchymal stem cells (MSCs/PVLA) via the bioconjugation of MSCs and reactive oxygen species-responsive polymeric micelles loaded with vactosertib (VST) and linifanib (LFN) for treating refractory asthma through reversing airway remodeling. MSCs/PVLA migrated to the tracheal lumen due to the inflammation tropism of MSCs, and subsequently released VST and LFN could inhibit the formation of airway remodeling by preventing subepithelial fibrosis and angiogenesis. Meanwhile, MSCs reduced inflammatory cell infiltration and cytokine secretion to regulate the pathological microenvironment. Our results suggested that MSCs/PVLA could serve as a promising candidate to prevent disease exacerbations and treat refractory asthma.

2024-06-01·World Neurosurgery

Venous Sinus Thrombosis–Associated with Posterior Cranial Fossa Surgery. A Systematic Review and Meta-Analysis of Natural History, Risk Factors, Treatment, and Outcome

Review

作者: Trevisi, Gianluca ; Auricchio, Anna Maria ; Ciaffi, Gabriele ; Sturiale, Carmelo Lucio ; Giovanni, Pennisi

BACKGROUNDVenous sinus thromboses (VSTs) are rare complications of neurosurgical procedures in the proximity of the dural sinuses. Surgery of the posterior cranial fossa (PCF) and particularly of the cerebellopontine angle (CPA) shows increased risk of VST. VST management is challenging because anticoagulant therapy must be balanced with the risk of postoperative bleeding. We performed a systematic review and meta-analysis to summarize the most important neuroradiologic and clinical aspects of VST after PCF/CPA surgery.METHODSWe performed a comprehensive literature search to identify articles reporting data on VST after PCF/CPA surgery. We selected only comparative studies providing adequate neuroimaging assessing VST and a control group.RESULTSWe included 13 articles reporting 1855 patients. VST occurred in 251/1855 cases (estimated incidence, 17.3%; 95% confidence interval [CI], 12.4%-22.2%). Only presigmoid approach (odds ratio [OR], 2.505; 95% CI, 1.161-5.404; P = 0.019) and intraoperative sinus injury (OR, 8.95; 95% CI, 3.43-23.34; P < 0.001) showed a significant association with VST. VST-related symptoms were reported in 12/251 patients with VST (pooled incidence, 3.1%; 95% CI, 1%-5.2%). In particular, we found a significantly increased OR of cerebrospinal fluid leak (OR, 3.197; 95% CI, 1.899-5.382; P < 0.001) and cerebrospinal fluid dynamic alterations in general (OR, 3.625; 95% CI, 2.370-5.543; P < 0.001). Indications for VST treatment were heterogeneous: 58/251 patients underwent antithrombotics, with 6 treatment-related bleedings. Recanalization overall occurred in 56.4% (95% CI, 40.6%-72.2%), with no significant difference between treated and untreated patients. However, untreated patients had a favorable outcome.CONCLUSIONSVST is a relatively frequent complication after PCF/CPA surgery and a presigmoid approach and intraoperative sinus injury represent the most significant risk factors. However, the clinical course is generally benign, with no advantage of antithrombotic therapy.

Nature Communications1区 · 综合性期刊

Secondary bone marrow graft loss after third-party virus-specific T cell infusion: Case report of a rare complication

1区 · 综合性期刊

ArticleOA

作者: Keller, Michael D ; Pulsipher, Michael A ; Chandrakasan, Shanmuganathan ; Lang, Haili ; Hanley, Patrick J ; Parikh, Suhag ; Tanna, Jay ; Bollard, Catherine M ; Berger, Seth I ; Jensen-Wachspress, Mariah A ; Allen, E Kaitlynn ; Qayed, Muna ; Gottschalk, Stephen ; Schattgen, Stefan A ; Pai, Sung-Yun ; Lazarski, Christopher A ; Thomas, Paul G

AbstractVirus-specific T cells (VST) from partially-HLA matched donors have been effective for treatment of refractory viral infections in immunocompromised patients in prior studies with a good safety profile, but rare adverse events have been described. Here we describe a unique and severe adverse event of VST therapy in an infant with severe combined immunodeficiency, who receives, as part of a clinical trial (NCT03475212), third party VSTs for treating cytomegalovirus viremia following bone marrow transplantation. At one-month post-VST infusion, rejection of graft and reversal of chimerism is observed, as is an expansion of T cells exclusively from the VST donor. Single-cell gene expression and T cell receptor profiling demonstrate a narrow repertoire of predominantly activated CD4+ T cells in the recipient at the time of rejection, with the repertoire overlapping more with that of peripheral blood from VST donor than the infused VST product. This case thus demonstrates a rare but serious side effect of VST therapy.

项与 Viral specific VST(Children's National Research Institute) 相关的新闻（医药）

2023-06-07

·药明康德

速递 | 有效预防6种病毒感染，现货型细胞疗法2期研究显示出积极疗效

▎药明康德内容团队编辑日前，AlloVir发布了旗下在研同种异体、现货型多病毒特异性T细胞（VST）疗法posoleucel用于治疗成年肾移植患者的BK病毒血症的临床2期研究的最终结果。这些发现支持了posoleucel在BK病毒（BKV）感染的成年肾移植患者中的安全性和抗病毒活性。目前，尚无有效的BKV感染治疗方法。BKV感染对肾移植存活构成重大威胁。每年全球范围内进行的肾移植手术超过9万例，其中多达20%的患者体内的BKV病毒会再度活化。在那些BKV已重新激活的患者中，大部分人会发展为高水平的病毒血症。其中约一半的人将会发展为与BKV相关的肾病（BKVAN），这可能导致肾存活率降低并引发终末期肾病和透析。目前没有获批的或有效的抗BKV感染治疗方法。管理BKV感染的唯一方法是减少免疫抑制以允许身体的免疫系统对抗病毒，这种免疫反应通常是由接近或超过每毫升1万个拷贝数的血浆BK病毒载量触发的。然而，免疫抑制的减少也可能导致由异源反应性T细胞介导的移植物排斥以及移植物特异性抗体的产生，从而影响肾移植的成功概率。BK病毒特异性T细胞似乎在防止这类疾病的发生中起关键作用。没有发展为BKVAN的肾移植患者已被证明比那些发展为BKVAN的患者拥有大约10倍的BKV特异性T细胞反应。罹患BK病毒血症的肾移植患者，如果能产生强大的BKV特异性T细胞反应，也能清除病毒，而那些发展为BKVAN的人则需要进行减少免疫抑制的医疗干预。这些数据暗示，VST疗法可能有助于管理BKV感染和BKVAN。AlloVir的主要产品posoleucel是一种同种异体、现货型、可针对六种病毒病原体的多病毒特异性T细胞疗法，目前正在进行后期临床开发。它所针对的六种病毒是：腺病毒（AdV）、BKV、巨细胞病毒（CMV）、爱泼斯坦-巴尔病毒（EBV）、人类疱疹病毒-6（HHV-6）和JC病毒（JCV）。在posoleucel的2期开放标签研究中，接受posoleucel治疗的同种异体造血细胞移植（allo-HCT）患者有88%在14周内没有出现临床重大感染（主要终点），该试验旨在预防posoleucel靶向的六种病毒引起的临床重大感染。而且，接受posoleucel治疗的患者在52周的随访期间，非复发性死亡率为0%。此外，这项研究纳入了被posoleucel靶向的六种病毒中的一种或多种感染的allo-HCT患者，超过90%未能接受常规治疗的患者接受了posoleucel治疗，这些患者在预设的标准上显示出完全或部分的临床缓解。这项2期研究评估了posoleucel治疗成年肾移植患者BKV感染的安全性和有效性，这些患者的血浆BK病毒载量在每毫升350-1千万个拷贝之间。包括美国肾脏病学会和美国移植学会在内的共识组认为，BK病毒载量大于或等于每毫升1万个拷贝数被认为是疑似BKVAN。该研究的主要终点是比较接受posoleucel和安慰剂治疗患者的安全性和耐受性，次要终点是接受posoleucel和接受安慰剂治疗的患者的BK病毒载量变化。今年早些时候，该研究的最初结果已经公开。基于posoleucel的2期临床研究数据对病毒预防和治疗的强大支持，FDA已授予posoleucel再生医学先进疗法（RMAT）认定，用于正处于3期临床试验阶段的三个适应症——治疗由BKV引起的出血性膀胱炎（HC）、治疗allo-HCT后成年人和儿童的AdV感染，以及预防posoleucel的六种目标病毒引起的临床重大感染和疾病。FDA还授予posoleucel治疗病毒相关HC的孤儿药物资格。欧洲药品管理局（EMA）已为posoleucel授予PRIME资格，用于治疗AdV、BKV、CMV、EBV和HHV-6的严重感染，并授予孤儿药资格，作为治疗接受HCT患者的病毒疾病和感染的潜在治疗方法。大家都在看▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料：[1] AlloVir Presents Positive Final Results From A Phase 2 Randomized, Placebo-Controlled Trial Evaluating Posoleucel Treatment of BK Infection in Kidney Transplant Recipients at the American Transplant Congress (ATC 2023)，Retrieved June 6, 2023, from https://www.businesswire.com/news/home/20230605005273/en/AlloVir-Presents-Positive-Final-Results-From-A-Phase-2-Randomized-Placebo-Controlled-Trial-Evaluating-Posoleucel-Treatment-of-BK-Infection-in-Kidney-Transplant-Recipients-at-the-American-Transplant-Congress-ATC-2023免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床2期细胞疗法临床1期

100 项与 Viral specific VST(Children's National Research Institute) 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
腺病毒科感染	临床1期	美国	Children's Research Institute, Inc.	2017-02-15
骨髓移植排斥反应	临床1期	美国	Children's Research Institute, Inc.	2017-02-15
爱泼斯坦-巴尔病毒感染	临床1期	美国	Children's Research Institute, Inc.	2017-02-15
移植物抗宿主病	临床1期	美国	Children's Research Institute, Inc.	2017-02-15
出血性膀胱炎	临床1期	美国	Children's Research Institute, Inc.	2017-02-15
肾脏疾病	临床1期	美国	Children's Research Institute, Inc.	2017-02-15
进行性多病灶脑白质病	临床1期	美国	Children's Research Institute, Inc.	2017-02-15