Macrophage Therapy for Acute Liver Failure

巨噬细胞治疗急性肝衰竭

基本信息

  • 批准号:
    MR/T044802/1
  • 负责人:
  • 金额:
    $ 339.65万
  • 依托单位:
  • 依托单位国家:
    英国
  • 项目类别:
    Research Grant
  • 财政年份:
    2020
  • 资助国家:
    英国
  • 起止时间:
    2020 至 无数据
  • 项目状态:
    未结题

项目摘要

Need: Acute liver failure (ALF) has no effective treatment other than liver transplantation, which has limited use because of its associated morbidity/mortality, expense to the health provider and the scarcity of donor livers. Paracetamol(acetaminophen) overdose is the commonest cause in the Western world. The only treatment for paracetamol overdose is acetylcysteine, which is preventative with regard to ALF only if treatment starts soon after overdose (within around 8h). For other causes of ALF there is currently no specific treatments. Solution: The proposed product is an off-the-shelf, allogeneic, alternatively-activated, macrophage cell therapy derived from 'universal' blood group O donor monocytes requiring no further matching of donor to recipient. The product will be frozen, stored close to the point of treatment and thawed on demand prior to infusion.Rationale: Alternatively-activated macrophages reduce liver necrosis and inflammatory cytokines, and increase proliferating hepatic progenitors in mouse models of ALF. Our solution is anchored by these world-leading pre-clinical studies, success in delivering macrophage therapy to patients with chronic liver disease (MATCH Trial, supported by DPFS, Moroni et al. Nature Medicine 2019) and the recent completion of the first phase 1 trial in paracetamol toxicity (Lancet EBioMedicine 2019 https://www.ebiomedicine.com/article/S2352).Development plan: In the first 18 months we will complete the IMPD and obtain a clinical trial authorisation. This process will be guided by the Cell and Gene Therapy Catapult and builds on our previous success with CTA applications for macrophage cell therapy in liver disease. In the following 30 months will deliver a phase 1 clinical trial of allogeneic, alternatively activated, macrophages in a phase 1 clinical trial in patients with paracetamol-induced acute liver injury. This builds on the unique local expertise in clinical trials of macrophage cell therapy in chronic liver disease and phase 1 clinical trials in acute paracetamol overdose.If successful this study paves the way for a randomised controlled trial of macrophage cell therapy for this condition and importantly will facilitate the development of macrophage cell therapy for other causes of acute liver failure.
需求:急性肝衰竭(ALF)除了肝移植外没有其他有效的治疗方法,肝移植由于其相关的发病率/死亡率、医疗提供者的费用和供体肝脏的稀缺而使用有限。扑热息痛(对乙酰氨基酚)过量是西方世界最常见的原因。对乙酰氨基酚过量的唯一治疗方法是乙酰半胱氨酸,只有在过量后不久(约8小时内)开始治疗时,乙酰半胱氨酸才能预防ALF。对于ALF的其他原因,目前没有具体的治疗方法。解决方法:申报产品是一种现成的、同种异体的、替代活化的巨噬细胞疗法,来源于“通用”O型血供体单核细胞,无需进一步匹配供体与受体。该产品将被冷冻,储存在治疗点附近,并在输注前按需解冻。理由:替代激活的巨噬细胞减少肝坏死和炎性细胞因子,并增加ALF小鼠模型中增殖的肝祖细胞。我们的解决方案以这些世界领先的临床前研究为基础,成功地为慢性肝病患者提供巨噬细胞治疗(MATCH试验,由DPFS支持,Moroni et al. Nature Medicine 2019)和最近完成的第一项对乙酰氨基酚毒性I期试验(柳叶刀EBioMedicine 2019 https://www.ebiomedicine.com/article/S2352)。开发计划:在前18个月内,我们将完成IMPD并获得临床试验授权。这一过程将由细胞和基因治疗弹射器指导,并建立在我们之前在肝脏疾病巨噬细胞治疗中CTA应用的成功基础上。在接下来的30个月内,将在对乙酰氨基酚诱导的急性肝损伤患者中进行同种异体替代活化巨噬细胞的1期临床试验。这是建立在巨噬细胞治疗慢性肝病的临床试验和急性扑热息痛过量的1期临床试验的独特本地专业知识基础上的。如果成功,这项研究将为巨噬细胞治疗这种疾病的随机对照试验铺平道路,重要的是将促进巨噬细胞治疗急性肝衰竭的其他原因的发展。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
No action is without its side effects: Adverse drug reactions and missed doses of antituberculosis therapy, a scoping review.
没有任何行动是没有副作用的:药物不良反应和错过的抗结核治疗剂量,范围审查。
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Stuart Forbes其他文献

Liver regeneration and inflammation: from fundamental science to clinical applications
肝脏再生与炎症:从基础科学到临床应用
  • DOI:
    10.1038/s41580-021-00373-7
  • 发表时间:
    2021-06-02
  • 期刊:
  • 影响因子:
    90.200
  • 作者:
    Lara Campana;Hannah Esser;Meritxell Huch;Stuart Forbes
  • 通讯作者:
    Stuart Forbes
3059 – VASCULAR SMOOTH MUSCLE CELLS EXPRESSING RUNX1 CONTROL HEMATOPOIESIS BY MODULATING EXTRACELLULAR MATRIX COMPOSITION IN THE MOUSE EMBRYO
  • DOI:
    10.1016/j.exphem.2022.07.115
  • 发表时间:
    2022-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Mihaela Crisan;Zaniah Gonzalez;Alastair Kilpatrick;Madalena marques;Diana Sa da bandeira;Telma Ventura;Mario Gomez-salazar;lea Bouilleau;Yvan Marc;Ana barbosa;Fiona Rossi;Mariana Beltran;Neil Henderson;harmen van de Werken;Wilfred van IJken;Stuart Forbes
  • 通讯作者:
    Stuart Forbes
Understanding the dynamic haematopoietic and mesenchymal stem cell contribution to the tumour microenvironment of cholangiocarcinoma
  • DOI:
    10.1016/j.ijsu.2012.06.026
  • 发表时间:
    2012-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Andrew Robson;Kay Samuel;Antonella Pellicoro;John Iredale;Stuart Forbes
  • 通讯作者:
    Stuart Forbes
OS117 - Primary cilia in biliary regeneration-a potential approach to improve outcomes in liver transplantation
OS117 - 胆道再生中的初级纤毛 - 一种改善肝移植结果的潜在方法
  • DOI:
    10.1016/s0168-8278(22)00563-3
  • 发表时间:
    2022-07-01
  • 期刊:
  • 影响因子:
    33.000
  • 作者:
    Hannah Esser;Sofia Ferreira-Gonzalez;Tak Yung Man;Alastair Kilpatrick;Daniel Rodrigo Torres;Rhona E. Aird;Candice Ashmore-Harris;Kayleigh Thirlwell;Benjamin J. Dwyer;Gabriel Oniscu;Stefan Schneeberger;Luke Boulter;Stuart Forbes
  • 通讯作者:
    Stuart Forbes
3060 – PDGFRΒ+ CELLS PLAY A DUAL ROLE AS HEMATOPOIETIC PRECURSORS AND NICHE CELLS DURING MOUSE ONTOGENY
  • DOI:
    10.1016/j.exphem.2022.07.116
  • 发表时间:
    2022-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Mihaela Crisan;Diana Sa da bandeira;Alastair Kilpatrick;Madalena Marques;Mario Gomez-salazar;Telma Ventura;Zaniah Gonzalez;Dorota Stefancova;Fiona Rossi;Chris Vink;Mariana Beltran;Neil Henderson;Bongnam Jung;Reinier Van Der Linden;Harmen Van De Werken;Wilfred Van IJcken;Christer Betsholtz;Stuart Forbes;Henar Cuervo
  • 通讯作者:
    Henar Cuervo

Stuart Forbes的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Stuart Forbes', 18)}}的其他基金

MRC IAA 2021 University of Edinburgh
MRC IAA 2021 爱丁堡大学
  • 批准号:
    MR/X502819/1
  • 财政年份:
    2022
  • 资助金额:
    $ 339.65万
  • 项目类别:
    Research Grant
UKRMP Hub: The Engineered Cell Environment.
UKRMP 中心:工程细胞环境。
  • 批准号:
    MR/R015635/1
  • 财政年份:
    2018
  • 资助金额:
    $ 339.65万
  • 项目类别:
    Research Grant
Defining the regenerative capacity of ductular cells from non-transplantable human liver
定义不可移植的人肝脏导管细胞的再生能力
  • 批准号:
    MR/P016839/1
  • 财政年份:
    2017
  • 资助金额:
    $ 339.65万
  • 项目类别:
    Research Grant
Autologous Macrophage Therapy for Liver Cirrhosis
自体巨噬细胞治疗肝硬化
  • 批准号:
    MR/M007588/1
  • 财政年份:
    2015
  • 资助金额:
    $ 339.65万
  • 项目类别:
    Research Grant
The Computational and Chemical Biology of the Stem Cell Niche
干细胞生态位的计算和化学生物学
  • 批准号:
    MR/L012766/1
  • 财政年份:
    2014
  • 资助金额:
    $ 339.65万
  • 项目类别:
    Research Grant
A hub for Engineering and exploiting the stem cell niche
工程和开发干细胞生态位的中心
  • 批准号:
    MR/K026666/1
  • 财政年份:
    2013
  • 资助金额:
    $ 339.65万
  • 项目类别:
    Research Grant
Automated delivery of high-viability therapeutic cell populations following revival from cryopreservation
冷冻保存复苏后自动输送高活力治疗细胞群
  • 批准号:
    MR/K500756/1
  • 财政年份:
    2012
  • 资助金额:
    $ 339.65万
  • 项目类别:
    Research Grant
Defining The Macrophage-Regulatory T Cell Axis That Promotes Fibrosis Resolution in the Liver
定义促进肝脏纤维化消退的巨噬细胞调节 T 细胞轴
  • 批准号:
    MR/J010766/1
  • 财政年份:
    2012
  • 资助金额:
    $ 339.65万
  • 项目类别:
    Research Grant
Autologous macrophage therapy promotes stem cell-mediated liver regeneration:a novel therapy for end-stage liver disease
自体巨噬细胞治疗促进干细胞介导的肝再生:终末期肝病的新疗法
  • 批准号:
    G1000868/1
  • 财政年份:
    2011
  • 资助金额:
    $ 339.65万
  • 项目类别:
    Research Grant

相似海外基金

ICF: Chimeric antigen receptor T cells targeting CD123, CD33 and CLL1 for therapy of Acute Myeloid Leukaemia
ICF:靶向 CD123、CD33 和 CLL1 的嵌合抗原受体 T 细胞用于治疗急性髓系白血病
  • 批准号:
    MR/X03030X/1
  • 财政年份:
    2023
  • 资助金额:
    $ 339.65万
  • 项目类别:
    Research Grant
New mechanism-based TREM-1 therapy for acute respiratory distress syndrome
基于新机制的 TREM-1 疗法治疗急性呼吸窘迫综合征
  • 批准号:
    10678788
  • 财政年份:
    2023
  • 资助金额:
    $ 339.65万
  • 项目类别:
Artificial Intelligence to Predict Outcomes in Patients with Acute Kidney Injury on Continuous Renal Replacement Therapy
人工智能预测急性肾损伤患者连续肾脏替代治疗的结果
  • 批准号:
    10658576
  • 财政年份:
    2023
  • 资助金额:
    $ 339.65万
  • 项目类别:
DEVELOPMENT OF PLX-R18 CELL THERAPY AS A COUNTERMEASURE FOR HEMATOPOIETIC ACUTE RADIATION SYNDROME
开发 PLX-R18 细胞疗法作为造血急性辐射综合征的对策
  • 批准号:
    10932592
  • 财政年份:
    2023
  • 资助金额:
    $ 339.65万
  • 项目类别:
Pharmacokinetic / Pharmacodynamic Optimization of ADC Therapy for Acute Myeloid Leukemia
急性髓系白血病 ADC 治疗的药代动力学/药效学优化
  • 批准号:
    10561230
  • 财政年份:
    2023
  • 资助金额:
    $ 339.65万
  • 项目类别:
Multi-institutional validation of a multi-modal machine learning algorithm to predict and reduce acute care during cancer therapy
对多模式机器学习算法进行多机构验证,以预测和减少癌症治疗期间的急性护理
  • 批准号:
    10587221
  • 财政年份:
    2023
  • 资助金额:
    $ 339.65万
  • 项目类别:
Development of tumor-immunoprofiling to predict therapy response against acute lymphoblastic leukemia
开发肿瘤免疫分析来预测急性淋巴细胞白血病的治疗反应
  • 批准号:
    23K15299
  • 财政年份:
    2023
  • 资助金额:
    $ 339.65万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Optimizing outcomes for children and young adults with relapse of B-cell acute lymphoblastic leukemia after CD19-targeted chimeric antigen receptor T-cell therapy
优化 CD19 靶向嵌合抗原受体 T 细胞治疗后 B 细胞急性淋巴细胞白血病复发的儿童和年轻人的结局
  • 批准号:
    10572071
  • 财政年份:
    2023
  • 资助金额:
    $ 339.65万
  • 项目类别:
Development of drug therapy targeting ferroptosis, iron-dependent cell death for acute respiratory distress syndrome.
开发针对铁死亡(急性呼吸窘迫综合征的铁依赖性细胞死亡)的药物疗法。
  • 批准号:
    23K08360
  • 财政年份:
    2023
  • 资助金额:
    $ 339.65万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Racial Differences in Hospital-Associated Disability and Acute and Post-Acute Care Physical Therapy Utilization
医院相关残疾以及急性和急性后护理物理治疗利用的种族差异
  • 批准号:
    10785500
  • 财政年份:
    2023
  • 资助金额:
    $ 339.65万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了