Therapeutically harnessing anti-viral resident memory T cells in solid tumors

利用抗病毒驻留记忆 T 细胞治疗实体瘤

基本信息

  • 批准号:
    10586695
  • 负责人:
  • 金额:
    $ 50.67万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-01-01 至 2027-12-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY/ABSTRACT Recent studies have revealed an abundance of resident memory T cells (TRM) specific for viral infections in a wide range of tumors, often outnumbering cancer-specific T cells. As these cells lack specificity to tumor antigens, they are spared from the hallmark exhaustion/dysfunction of tumor-specific T cells. To this end, we developed a novel immunotherapy which taps into immunostimulatory virus-specific TRM functions through treatment with viral peptides to break the immunosuppressive tumor environment. Reactivating virus-specific TRM with peptide was sufficient to restrict tumor growth in mice and when combined with checkpoint blockade, promoted durable tumor clearance. Mice that cleared tumors were protected from tumor re-challenge, suggesting anti-tumor immunity was established. Virus-specific TRM represent a major part of the tumor immune environment and can be leveraged therapeutically, yet there is a clinically significant gap in knowledge regarding the mechanisms of tumor clearance and how to optimally harness these cells. The objectives in this proposal are to determine (i) mechanism of tumor cell killing and durable tumor immunity, (ii) the impact of viral specificity on TRM function and therapeutic efficacy, and iii) define the optimal modality to reactivate virus-specific TRM. Using both mouse and human systems, this study addresses an innovative perspective connecting antiviral memory cells to tumor immunotherapy using cutting edge methods. We will complement mouse studies with combinatorial tetramer staining to enable simultaneous profiling of T cells specific for an expanded panel of viruses and vaccines in patient tumors. Completion of these aims will advance our understanding of tumor immunosurveillance and TRM function in mice and humans, and identify new target T cell populations for tumor immunotherapy. This contribution is expected to be significant because it will provide a strong scientific framework to expand the efficacy and utility of virus-specific TRM therapy, and enable the development of novel strategies leveraging these potent immune activating cells.
项目概要/摘要 最近的研究表明,体内存在大量针对病毒感染的常驻记忆 T 细胞 (TRM)。 广泛的肿瘤,通常超过癌症特异性 T 细胞。由于这些细胞缺乏针对肿瘤的特异性 抗原,它们不会出现肿瘤特异性 T 细胞的标志性耗竭/功能障碍。为此,我们 开发了一种新型免疫疗法,通过以下方式利用免疫刺激病毒特异性 TRM 功能 用病毒肽治疗以打破免疫抑制肿瘤环境。重新激活病毒特异性 含有肽的 TRM 足以限制小鼠体内的肿瘤生长,并且当与检查点阻断相结合时, 促进持久的肿瘤清除。清除肿瘤的小鼠免受肿瘤的再次攻击,这表明 建立了抗肿瘤免疫力。病毒特异性 TRM 代表肿瘤免疫环境的主要部分 并且可以在治疗上利用,但临床上在这方面的知识还存在重大差距 肿瘤清除机制以及如何最佳地利用这些细胞。本提案的目标是 确定(i)肿瘤细胞杀伤机制和持久的肿瘤免疫,(ii)病毒特异性对肿瘤细胞的影响 TRM 功能和治疗功效,以及 iii) 定义重新激活病毒特异性 TRM 的最佳方式。使用 无论是小鼠还是人类系统,这项研究提出了连接抗病毒记忆的创新视角 使用尖端方法进行细胞肿瘤免疫治疗。我们将补充小鼠研究 组合四聚体染色可同时对扩展的一组 T 细胞进行分析 患者肿瘤中的病毒和疫苗。完成这些目标将增进我们对肿瘤的理解 小鼠和人类的免疫监视和 TRM 功能,并确定肿瘤的新靶 T 细胞群 免疫疗法。预计这一贡献将是重大的,因为它将提供强有力的科学依据 框架,以扩大病毒特异性 TRM 疗法的功效和效用,并促进新型药物的开发 利用这些有效的免疫激活细胞的策略。

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 }}

Pamela Rosato其他文献

Pamela Rosato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('Pamela Rosato', 18)}}的其他基金

Investigating virus- and vaccine-specific T cells in glioblastoma
研究胶质母细胞瘤中病毒和疫苗特异性 T 细胞
  • 批准号:
    10817478
  • 财政年份:
    2023
  • 资助金额:
    $ 50.67万
  • 项目类别:
The role of brain resident T cells in Alzheimer's disease
大脑常驻 T 细胞在阿尔茨海默病中的作用
  • 批准号:
    10693931
  • 财政年份:
    2022
  • 资助金额:
    $ 50.67万
  • 项目类别:
The role of brain resident T cells in Alzheimer's disease
大脑常驻 T 细胞在阿尔茨海默病中的作用
  • 批准号:
    10515916
  • 财政年份:
    2022
  • 资助金额:
    $ 50.67万
  • 项目类别:
Function and regulation of brain resident memory T cells
大脑常驻记忆T细胞的功能和调节
  • 批准号:
    10350543
  • 财政年份:
    2021
  • 资助金额:
    $ 50.67万
  • 项目类别:
Function and regulation of brain resident memory T cells
大脑常驻记忆T细胞的功能和调节
  • 批准号:
    9870360
  • 财政年份:
    2021
  • 资助金额:
    $ 50.67万
  • 项目类别:
Impact of pre-existing T cell memory on oncolytic virus therapy
预先存在的 T 细胞记忆对溶瘤病毒治疗的影响
  • 批准号:
    10226591
  • 财政年份:
    2020
  • 资助金额:
    $ 50.67万
  • 项目类别:
Impact of pre-existing T cell memory on oncolytic virus therapy
预先存在的 T 细胞记忆对溶瘤病毒治疗的影响
  • 批准号:
    10271750
  • 财政年份:
    2016
  • 资助金额:
    $ 50.67万
  • 项目类别:
Impact of pre-existing T cell memory on oncolytic virus therapy
预先存在的 T 细胞记忆对溶瘤病毒治疗的影响
  • 批准号:
    10460276
  • 财政年份:
    2016
  • 资助金额:
    $ 50.67万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 50.67万
  • 项目类别:
    Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 50.67万
  • 项目类别:
    Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 50.67万
  • 项目类别:
    Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 50.67万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 50.67万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 50.67万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 50.67万
  • 项目类别:
    EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 50.67万
  • 项目类别:
    Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 50.67万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 50.67万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了