Allogeneic antibody therapy for malignant mesothelioma

恶性间皮瘤的同种异体抗体治疗

基本信息

  • 批准号:
    9101172
  • 负责人:
  • 金额:
    $ 7.93万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-04-01 至 2018-03-31
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Tumors progress through evasion of the immune system. In contrast to autologous (self) tumors, allogeneic (non-self) tumors, like organ transplants, are rejected when transferred into immunologically normal hosts. Our studies performed to understand this process of non-self tumor rejection has identified a critical role for allogeneic IgG antibodies (alloIgG) in the recognition of tumor cells, and in the generation of a powerful anti- tumor immune response. We have found that when alloIgG is combined with a dendritic cell (DC) stimulant and injected into a variety of mouse tumors including melanoma, breast, pancreas and lung carcinoma, that these tumors are eradicated, with little or no side effects. Importantly, we have found that IgG antibodies from healthy donors recognize tumor cells from obtained from patients undergoing surgical resection for mesothelioma and lung cancer, and that these antibodies can activate anti-tumor human immune responses, in vitro. The objective of this application is to obtain the preclinical data necessary to provide the rationale and feasibility for a future phase I clinical trial that will be designed to use alloIgG therapy for treatment of malignant pleural mesothelioma. We will use a well-established preclinical model of mesothelioma, and freshly isolated tumor cells and immune cells from patients undergoing surgical resection of mesothelioma to determine the critical elements of this trial: (1) the most efficacious DC stimulant, (2) the most efficacious source of IgG, and (3) the most efficacious route and schedule of administration of alloIgG. To facilitate rapid translation o this novel immune-based technology into the clinic, we are focusing our appraisal of DC stimulants to agents that have been approved by the FDA, and we will also test commercially available formulations of intravenous immunoglobulins (IVIG) that are FDA-approved and generally comprise pooled IgG antibodies from more than 10,000 donors. At the conclusion of this study, we will have defined a clinical grade alloantibody formulation that comprises an appropriate DC stimulant and a source of IgG, and for which we will submit IND applications for a clinical trial. In Aim 1 we will test a variety of DC stimulants in a preclinical, immunologicall intact, mouse model of malignant mesothelioma, and then test the ability of these agents to activate tumor-associated DC freshly isolated from mesothelioma tumors, freshly obtained at the time of surgical resection. In Aim 2, we will use similar human tumor-associated DC assays to determine the most effective formulation of IgG (IVIG or pooled IgG obtained from healthy donors), and we will use our mouse model to determine the most effective route (local versus intravenous) and schedule (single versus multiple cycles) of alloIgG administration. Our findings will advance the understanding of alloIgG therapy for solid tumors, and will facilitate the design of an early phase, first-in-man, clinical trial using this novel immunotherapy.
 描述(由申请人提供):肿瘤通过逃避免疫系统而进展。与自体(自身)肿瘤相反,同种异体(非自身)肿瘤,如器官移植,当转移到免疫正常的宿主时会被排斥。我们的研究旨在了解这种非自体肿瘤排斥反应的过程,已经确定了免疫抑制的关键作用。 同种IgG抗体(alloIgG)在识别肿瘤细胞,并产生强大的抗肿瘤免疫应答中发挥重要作用。我们已经发现,当alloIgG与树突状细胞(DC)刺激剂组合并注射到各种小鼠肿瘤(包括黑素瘤、乳腺癌、胰腺癌和肺癌)中时,这些肿瘤被根除,副作用很小或没有副作用。重要的是,我们发现来自健康供体的IgG抗体识别从经历间皮瘤和肺癌手术切除的患者获得的肿瘤细胞,并且这些抗体可以在体外激活抗肿瘤人类免疫应答。本申请的目的是获得必要的临床前数据,以提供未来I期临床试验的原理和可行性,该临床试验将设计用于使用alloIgG治疗恶性胸膜间皮瘤。我们将使用完善的间皮瘤临床前模型,以及从接受间皮瘤手术切除的患者中新鲜分离的肿瘤细胞和免疫细胞来确定本试验的关键要素:(1)最有效的DC刺激剂,(2)最有效的IgG来源,以及(3)最有效的alloIgG给药途径和时间表。为了促进这种基于免疫的新技术快速转化为临床,我们将重点评估已获FDA批准的DC刺激剂,我们还将测试市售的静脉内免疫球蛋白(IVIG)制剂,这些制剂已获FDA批准,通常包含来自10,000多名供体的合并IgG抗体。在本研究结束时,我们将确定一种临床级同种抗体制剂,该制剂包含适当的DC刺激剂和IgG来源,我们将提交IND申请进行临床试验。在目的1中,我们将在临床前、免疫完整的恶性间皮瘤小鼠模型中测试多种DC刺激剂,然后测试这些药剂激活从间皮瘤肿瘤新鲜分离的肿瘤相关DC的能力,所述肿瘤相关DC在手术切除时新鲜获得。在目标2中,我们将使用类似的人肿瘤相关DC测定来确定IgG的最有效制剂(IVIG或从健康供体获得的合并IgG),并且我们将使用我们的小鼠模型来确定最有效的alloIgG施用途径(局部与静脉内)和时间表(单周期与多周期)。我们的研究结果将促进对实体瘤alloIgG治疗的理解,并将有助于设计使用这种新型免疫疗法的早期、首次人体临床试验。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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

{{ 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 }}

Bryan Michael Burt其他文献

Bryan Michael Burt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('Bryan Michael Burt', 18)}}的其他基金

Validation and Translation of MasSpec Pen Technology for Intraoperative Evaluation of Non-small Cell Lung Cancer
MasSpec Pen 技术在非小细胞肺癌术中评估中的验证和转化
  • 批准号:
    10753977
  • 财政年份:
    2023
  • 资助金额:
    $ 7.93万
  • 项目类别:
Proteomic determinants of response to checkpoint blockade in malignant pleuralmesothelioma
恶性胸膜间皮瘤检查点阻断反应的蛋白质组决定因素
  • 批准号:
    10545173
  • 财政年份:
    2021
  • 资助金额:
    $ 7.93万
  • 项目类别:
Proteomic determinants of response to checkpoint blockade in malignant pleuralmesothelioma
恶性胸膜间皮瘤检查点阻断反应的蛋白质组决定因素
  • 批准号:
    10321963
  • 财政年份:
    2021
  • 资助金额:
    $ 7.93万
  • 项目类别:
Natural Killer Dendritic Cells in Cancer
癌症中的自然杀伤树突状细胞
  • 批准号:
    7156378
  • 财政年份:
    2006
  • 资助金额:
    $ 7.93万
  • 项目类别:
Natural Killer Dendritic Cells in Cancer
癌症中的自然杀伤树突状细胞
  • 批准号:
    7270486
  • 财政年份:
    2006
  • 资助金额:
    $ 7.93万
  • 项目类别:

相似海外基金

Unraveling Adverse Effects of Checkpoint Inhibitors Using iPSC-derived Cardiac Organoids
使用 iPSC 衍生的心脏类器官揭示检查点抑制剂的副作用
  • 批准号:
    10591918
  • 财政年份:
    2023
  • 资助金额:
    $ 7.93万
  • 项目类别:
Optimization of mRNA-LNP vaccine for attenuating adverse effects and analysis of mechanism behind adverse effects
mRNA-LNP疫苗减轻不良反应的优化及不良反应机制分析
  • 批准号:
    23K15383
  • 财政年份:
    2023
  • 资助金额:
    $ 7.93万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Elucidation of adverse effects of combined exposure to low-dose chemicals in the living environment on allergic diseases and attempts to reduce allergy
阐明生活环境中低剂量化学品联合暴露对过敏性疾病的不良影响并尝试减少过敏
  • 批准号:
    23H03556
  • 财政年份:
    2023
  • 资助金额:
    $ 7.93万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Green tea-based nano-enhancer as an adjuvant for amplified efficacy and reduced adverse effects in anti-angiogenic drug treatments
基于绿茶的纳米增强剂作为抗血管生成药物治疗中增强疗效并减少不良反应的佐剂
  • 批准号:
    23K17212
  • 财政年份:
    2023
  • 资助金额:
    $ 7.93万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Effects of Tobacco Heating System on the male reproductive function and towards to the reduce of the adverse effects.
烟草加热系统对男性生殖功能的影响以及减少不利影响。
  • 批准号:
    22H03519
  • 财政年份:
    2022
  • 资助金额:
    $ 7.93万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Mitigating the Adverse Effects of Ultrafines in Pressure Filtration of Oil Sands Tailings
减轻油砂尾矿压力过滤中超细粉的不利影响
  • 批准号:
    563657-2021
  • 财政年份:
    2022
  • 资助金额:
    $ 7.93万
  • 项目类别:
    Alliance Grants
1/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
1/4-破译ECT结果和不良反应的机制(DECODE)
  • 批准号:
    10521849
  • 财政年份:
    2022
  • 资助金额:
    $ 7.93万
  • 项目类别:
4/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
4/4-破译ECT结果和不良反应的机制(DECODE)
  • 批准号:
    10671022
  • 财政年份:
    2022
  • 资助金额:
    $ 7.93万
  • 项目类别:
2/4 Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
2/4 ECT 结果和不良反应的破译机制(DECODE)
  • 批准号:
    10670918
  • 财政年份:
    2022
  • 资助金额:
    $ 7.93万
  • 项目类别:
Adverse Effects of Using Laser Diagnostics in High-Speed Compressible Flows
在高速可压缩流中使用激光诊断的不利影响
  • 批准号:
    RGPIN-2018-04753
  • 财政年份:
    2022
  • 资助金额:
    $ 7.93万
  • 项目类别:
    Discovery Grants Program - Individual
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了