Optimizing CAR T therapy via metabolic engineering for thetreatment of GBM

通过代谢工程优化 CAR T 疗法治疗 GBM

基本信息

  • 批准号:
    10722922
  • 负责人:
  • 金额:
    $ 17.82万
  • 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:
    2023-07-05 至 2025-06-30
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY AND ABSTRACT Significance: Glioblastoma (GBM) is an extremely devastating disease with reported median survivals ranging from 13 to 73 months and 5-year survivals of less than 20% in children and about 15 months with less than 5% 5-year survival rate for adult patients. Cancer immunotherapy using chimeric antigen receptor (CAR) modified T cells is a promising treatment, however its efficacy in GBM has been limited. Hypothesis: We hypothesize that the fierce competition for nutrients within the tumor microenvironment, especially glucose, between tumor cells and the immune system, imposes an abundant metabolic pressure to CAR T cells dampening their effector function and intratumoral infiltration, expansion, and persistence. Objective: The goal of this study is to validate a new strategy to overcome this metabolic imbalance and provide a competitive advantage to CAR T cells over tumor cells. We propose to improve CAR T cell therapy by enhancing metabolic fitness to outcompete GBM cells for nutrients like glucose. Methods: Our approach will be to directly target the first step of glucose metabolism (i.e., uptake) by permanent overexpression of GLUT1 or GLUT3 and generating the following CAR T cells: CD70CAR.G1 and CD70CAR.G3. The murine model of glioma KR158B, derived from Nf1;Trp53 mutant mouse, that we engineered to express CD70 as well as CD70 expressing human GBM patient-derived cell lines will be used for the following aims: Specific Aims 1. Investigate the phenotypic and functional characteristics of metabolically modified CD70CAR T cells, 2. Evaluate in vivo the metabolic TME of animals treated with CD70CAR.G1 or CD70CAR.G3, 3. Examine the safety and anti-tumor efficacy of CD70CAR.G1 or CD70CAR.G3.
项目总结和摘要 意义:胶质母细胞瘤(GBM)是一种极具破坏性的疾病,据报道, 儿童13至73个月和5年生存率低于20%,约15个月生存率低于5% 5-成年患者的年生存率。使用嵌合抗原受体(CAR)修饰的T细胞的癌症免疫疗法 细胞是一种有前途的治疗方法,但其在GBM中的疗效有限。 假设:我们假设肿瘤微环境中对营养物质的激烈竞争, 特别是葡萄糖,在肿瘤细胞和免疫系统之间,施加了大量的代谢压力, CAR T细胞抑制其效应子功能和肿瘤内浸润、扩增和持久性。 目的:本研究的目的是验证克服这种代谢失衡的新策略, CAR T细胞相对于肿瘤细胞的竞争优势。我们建议通过以下方式改善CAR T细胞疗法: 增强代谢适应性以在营养物如葡萄糖的竞争中胜过GBM细胞。 方法:我们的方法将直接针对葡萄糖代谢的第一步(即,吸收) G1和CD70CAR.G3。 神经胶质瘤小鼠模型KR 158 B,来源于Nf 1; Trp 53突变小鼠,我们设计表达 CD 70以及表达CD 70的人GBM患者来源细胞系将用于以下目的: 具体目标 1.研究代谢修饰的CD 70 CAR T细胞的表型和功能特征, 2.在体内评价用CD70CAR.G1或CD70CAR.G3处理的动物的代谢TME, 3.检查CD70CAR.G1或CD70CAR.G3的安全性和抗肿瘤疗效。

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 }}

Loic Pierre Deleyrolle其他文献

Loic Pierre Deleyrolle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('Loic Pierre Deleyrolle', 18)}}的其他基金

Metabolic interactions between tumor cells and the immunce system in GBM A potential Achilles heel of GBM for novel therapeutics
GBM 中肿瘤细胞与免疫系统之间的代谢相互作用是 GBM 新疗法的潜在致命弱点
  • 批准号:
    10522529
  • 财政年份:
    2022
  • 资助金额:
    $ 17.82万
  • 项目类别:
Metabolic interactions between tumor cells and the immunce system in GBM A potential Achilles heel of GBM for novel therapeutics
GBM 中肿瘤细胞与免疫系统之间的代谢相互作用是 GBM 新疗法的潜在致命弱点
  • 批准号:
    10673172
  • 财政年份:
    2022
  • 资助金额:
    $ 17.82万
  • 项目类别:
Slow cycling cell RNA based T cell therapy to prevent recurrence in GBM
基于慢循环细胞 RNA 的 T 细胞疗法可预防 GBM 复发
  • 批准号:
    10331046
  • 财政年份:
    2021
  • 资助金额:
    $ 17.82万
  • 项目类别:

相似海外基金

Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
  • 批准号:
    MR/Z503605/1
  • 财政年份:
    2024
  • 资助金额:
    $ 17.82万
  • 项目类别:
    Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
  • 批准号:
    2336167
  • 财政年份:
    2024
  • 资助金额:
    $ 17.82万
  • 项目类别:
    Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
  • 批准号:
    2402691
  • 财政年份:
    2024
  • 资助金额:
    $ 17.82万
  • 项目类别:
    Standard Grant
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
  • 批准号:
    2341428
  • 财政年份:
    2024
  • 资助金额:
    $ 17.82万
  • 项目类别:
    Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
  • 批准号:
    24K12150
  • 财政年份:
    2024
  • 资助金额:
    $ 17.82万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
  • 批准号:
    DE240100561
  • 财政年份:
    2024
  • 资助金额:
    $ 17.82万
  • 项目类别:
    Discovery Early Career Researcher Award
Laboratory testing and development of a new adult ankle splint
新型成人踝关节夹板的实验室测试和开发
  • 批准号:
    10065645
  • 财政年份:
    2023
  • 资助金额:
    $ 17.82万
  • 项目类别:
    Collaborative R&D
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
  • 批准号:
    23K09542
  • 财政年份:
    2023
  • 资助金额:
    $ 17.82万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
  • 批准号:
    23K07552
  • 财政年份:
    2023
  • 资助金额:
    $ 17.82万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
  • 批准号:
    23K07559
  • 财政年份:
    2023
  • 资助金额:
    $ 17.82万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了