Induction of autosis to overcome resistance in adoptive cell therapy for solid tumors
诱导自体死亡以克服实体瘤过继细胞治疗中的耐药性
基本信息
- 批准号:10629835
- 负责人:
- 金额:$ 58.33万
- 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:2023-04-01 至 2028-03-31
- 项目状态:未结题
- 来源:
- 关键词:Adoptive Cell TransfersAdoptive ImmunotherapyAntigen TargetingAntigensApoptosisCell DeathCellsClinical TrialsDNA VirusesDataEndowmentEuropeanEventExertionFoundationsFutureHeterogeneityHumanImmune responseImmunityImmunocompetentImmunologic Deficiency SyndromesIn VitroLeukocytesMalignant NeoplasmsMalignant neoplasm of ovaryMediatingModelingMolecularMusMyxoma virusNatureOncolytic virusesOryctolagus cuniculusPathogenicityPatientsProto-Oncogene Proteins c-aktRag1 MouseRecurrenceResistanceRoleSKOV3 cellsSignal TransductionSolid NeoplasmT-Cell ReceptorT-LymphocyteTestingTherapeutic IndexTumor AntigensTumor ImmunityViral load measurementWorkcell killingchimeric antigen receptorchimeric antigen receptor T cellscomplement C2aeffector T cellin vivomelanomamesothelinmouse modelneoplastic cellnovelpatient derived xenograft modelpre-clinicalpreventresponsesynergismtreatment responsetumortumor eradicationtumor heterogeneitytumor xenograft
项目摘要
Project Summary
Adoptive cell therapy is a promising approach to treat cancer, but despite tremendous efforts, results of clinical
trials in human solid tumors using ACT with tumor-specific T cells expressing T-cell-receptors (TCR) or
chimeric antigen receptors (CAR) have not demonstrated the desired therapeutic responses. Recently, we
developed tumor-specific T cells loaded with the myxoma virus to overcome resistance in solid tumor ACT. We
hypothesize that anti-solid tumor activity of these T cells is mainly attributed to a special type of tumor cell
death, autosis, that has not been considered a T cell killing mechanism before but may contribute to the
observed exciting antitumor potency by targeting both antigen-positive and antigen-negative tumor cells. Aim 1
will determine the unique molecular mechanism underlying tumor cell autosis induced by the synergy of
myxoma virus-derived factor(s) with T cell-derived soluble factor(s). Aim 2 will determine the role of these
tumor-specific T cells in promoting autosis and robust host immunity to eradicate solid tumors when the
targeted antigen is expressed by only ~25% of tumor cells. Our proposed studies will identify a novel ACT
strategy endowed with the capacity to eliminate solid tumors with very high antigen heterogeneity. This
translationally relevant work holds promise to significantly advance the therapeutic index of ACT in solid
tumors and could then lay the foundation for future clinical trials.
项目摘要
免疫细胞疗法是治疗癌症的一种有希望的方法,但是尽管做出了巨大的努力,临床结果仍然是不稳定的。
使用ACT与表达T细胞受体(TCR)的肿瘤特异性T细胞进行的人实体瘤试验,或
嵌合抗原受体(CAR)尚未显示出所需的治疗反应。最近我们
开发了负载粘液瘤病毒的肿瘤特异性T细胞,以克服实体瘤ACT的耐药性。我们
假设这些T细胞抗实体瘤活性主要归因于特殊类型的肿瘤细胞
死亡,自体免疫,以前没有被认为是T细胞杀伤机制,但可能有助于
通过靶向抗原阳性和抗原阴性肿瘤细胞,观察到令人兴奋的抗肿瘤效力。要求1
将确定肿瘤细胞自体化的独特分子机制,
粘液瘤病毒衍生的因子与T细胞衍生的可溶性因子。目标2将确定这些方面的作用
肿瘤特异性T细胞在促进自体免疫和强大的宿主免疫以根除实体瘤时,
靶向抗原仅由~25%的肿瘤细胞表达。我们提出的研究将确定一种新的ACT
该策略被赋予消除具有非常高抗原异质性的实体瘤的能力。这
临床相关工作有望显著提高ACT在固体中的治疗指数,
这将为未来的临床试验奠定基础。
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 }}
Yong Lu其他文献
Yong Lu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('Yong Lu', 18)}}的其他基金
Intrapleural immunotherapeutic nanoparticles for MPE treatment
用于 MPE 治疗的胸膜内免疫治疗纳米粒子
- 批准号:
10673709 - 财政年份:2021
- 资助金额:
$ 58.33万 - 项目类别:
The Unique Roles of Tumor-Specific Th9 Cells for Solid Tumor Eradication
肿瘤特异性 Th9 细胞在实体瘤根除中的独特作用
- 批准号:
10177223 - 财政年份:2021
- 资助金额:
$ 58.33万 - 项目类别:
Intrapleural immunotherapeutic nanoparticles for MPE treatment
用于 MPE 治疗的胸膜内免疫治疗纳米粒子
- 批准号:
10456907 - 财政年份:2021
- 资助金额:
$ 58.33万 - 项目类别:
The Unique Roles of Tumor-Specific Th9 Cells for Solid Tumor Eradication
肿瘤特异性 Th9 细胞在实体瘤根除中的独特作用
- 批准号:
10557757 - 财政年份:2021
- 资助金额:
$ 58.33万 - 项目类别:
The Unique Roles of Tumor-Specific Th9 Cells for Solid Tumor Eradication
肿瘤特异性 Th9 细胞在实体瘤根除中的独特作用
- 批准号:
10706513 - 财政年份:2021
- 资助金额:
$ 58.33万 - 项目类别:
Eradication of Escaped Variant Tumor Cells for Cancer Immunotherapy
根除逃逸变异肿瘤细胞以进行癌症免疫治疗
- 批准号:
10541139 - 财政年份:2021
- 资助金额:
$ 58.33万 - 项目类别:
Eradication of Escaped Variant Tumor Cells for Cancer Immunotherapy
根除逃逸变异肿瘤细胞以进行癌症免疫治疗
- 批准号:
10557758 - 财政年份:2021
- 资助金额:
$ 58.33万 - 项目类别:
Intrapleural immunotherapeutic nanoparticles for MPE treatment
用于 MPE 治疗的胸膜内免疫治疗纳米粒子
- 批准号:
10296779 - 财政年份:2021
- 资助金额:
$ 58.33万 - 项目类别:
P38 MAPK is a molecular switch that controls the acquired resistance in adoptive cell therapy
P38 MAPK 是一种分子开关,可控制过继性细胞疗法中的获得性耐药
- 批准号:
10028420 - 财政年份:2020
- 资助金额:
$ 58.33万 - 项目类别:
P38 MAPK is a molecular switch that controls the acquired resistance in adoptive cell therapy
P38 MAPK 是一种分子开关,可控制过继性细胞疗法中的获得性耐药
- 批准号:
10407010 - 财政年份:2020
- 资助金额:
$ 58.33万 - 项目类别:
相似海外基金
VLA-4–targeted 67Cu-LLP2A preconditioning enhances efficacy of T-cell-based adoptive immunotherapy
VLA-4™ 靶向 67Cu-LLP2A 预处理增强基于 T 细胞的过继免疫疗法的疗效
- 批准号:
10713034 - 财政年份:2023
- 资助金额:
$ 58.33万 - 项目类别:
Phase I first-in-human trial for ThINKK adoptive immunotherapy in children with high-risk cancers
针对高危癌症儿童的ThINKK过继免疫疗法的I期首次人体试验
- 批准号:
484371 - 财政年份:2023
- 资助金额:
$ 58.33万 - 项目类别:
Operating Grants
Phase I first-in-human trial of ThINKK adoptive immunotherapy in children with high-risk cancers
针对高危癌症儿童的ThINKK过继免疫疗法的I期首次人体试验
- 批准号:
473376 - 财政年份:2022
- 资助金额:
$ 58.33万 - 项目类别:
Operating Grants
Development of Adoptive Immunotherapy Focusing on Follicular Helper T Cell Biology
专注于滤泡辅助 T 细胞生物学的过继免疫疗法的发展
- 批准号:
21K16420 - 财政年份:2021
- 资助金额:
$ 58.33万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Mathematical Model-Guided Adoptive Immunotherapy in Bladder Cancer
数学模型引导的膀胱癌过继免疫治疗
- 批准号:
10180117 - 财政年份:2021
- 资助金额:
$ 58.33万 - 项目类别:
Mathematical Model-Guided Adoptive Immunotherapy in Bladder Cancer
数学模型引导的膀胱癌过继免疫治疗
- 批准号:
10364687 - 财政年份:2021
- 资助金额:
$ 58.33万 - 项目类别:
Mathematical Model-Guided Adoptive Immunotherapy in Bladder Cancer
数学模型引导的膀胱癌过继免疫治疗
- 批准号:
10599851 - 财政年份:2021
- 资助金额:
$ 58.33万 - 项目类别:
Elucidation of the function of the new NK cell subset and its application to adoptive immunotherapy
阐明新NK细胞亚群的功能及其在过继性免疫治疗中的应用
- 批准号:
21H04832 - 财政年份:2021
- 资助金额:
$ 58.33万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Development of a combinatorial approach of antibody therapeutics and adoptive immunotherapy for cancer
开发抗体疗法和癌症过继免疫疗法的组合方法
- 批准号:
21K19422 - 财政年份:2021
- 资助金额:
$ 58.33万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
Adoptive immunotherapy for adult T-cell leukemia/lymphoma with ex vivo expanded multi-tumor associated antigen specific cytotoxic T-cells
使用离体扩增的多肿瘤相关抗原特异性细胞毒性 T 细胞对成人 T 细胞白血病/淋巴瘤进行过继免疫治疗
- 批准号:
20K17375 - 财政年份:2020
- 资助金额:
$ 58.33万 - 项目类别:
Grant-in-Aid for Early-Career Scientists