Vista, A Novel Checkpoint that Suppresses Anti-Tumor T Cell Responses
Vista,一种抑制抗肿瘤 T 细胞反应的新型检查点
基本信息
- 批准号:9974483
- 负责人:
- 金额:$ 34.76万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-09-01 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:BindingBiochemicalCD8-Positive T-LymphocytesCTLA4 geneCell physiologyClinicalComplexDataDevelopmentDistalEnzymesEpitopesFoundationsFunctional disorderGoalsHumanImmunofluorescence ImmunologicImmunoglobulin DomainImpairmentKnockout MiceKnowledgeLeadLeucine-Rich RepeatLigandsMalignant NeoplasmsMediatingMolecularMonoclonal AntibodiesMusMutagenesisOutcomePathway interactionsPlayProteinsReagentReceptor ActivationRegulatory T-LymphocyteRoleSignal TransductionSignaling MoleculeSignaling ProteinSuppressor-Effector T-LymphocytesT cell responseT-Cell ActivationT-LymphocyteTestingTherapeuticTissuesTumor ImmunityTumor-associated macrophagesUbiquitinWorkcancer immunotherapycancer therapycheckpoint receptorscombinatorialconditional knockoutimmune checkpointinhibitor/antagonistleucine-rich repeat proteinmalignant breast neoplasmmutantnovelprogrammed cell death protein 1protein expressionreceptorrecruitsmall moleculetumor
项目摘要
Project Summary:
Immune-checkpoint receptors such as CTLA-4 and PD-1 have been successfully targeted for
cancer immunotherapy. Our earlier work has identified V domain Immunoglobulin Suppressor of
T cell Activation (VISTA) as an immune-checkpoint protein that critically regulates anti-tumor
immunity. Despite this progress, how VISTA inhibits T cell activation is not understood. Our
current study has identified a novel VISTA-interacting receptor that is expressed on murine and
human T cells and mediates the suppressive effect of VISTA. The overarching goals of this
proposal are to define the cellular and molecular mechanisms of this novel T cell coinhibitory
complex. Specific aim 1 will dissect the interactions between VISTA and its receptor and establish
the relevance of ubiquitin-modifying enzymes to the inhibitory signaling. Aim 2 will examine the
role of VISTA and its receptor in regulating tumor-specific T cell responses, utilizing a newly
generated conditional knockout mice and novel inhibitors that block this inhibitory receptor
complex. The protein expression level of VISTA and its receptor in human cancer tissues will also
be examined. Together, these proposed studies will build a foundation for developing novel
inhibitors that target the VISTA receptor complex for cancer immunotherapy.
项目概要:
免疫检查点受体如CTLA-4和PD-1已被成功靶向,
癌症免疫疗法我们早期的工作已经确定了V结构域免疫球蛋白抑制剂,
T细胞活化(VISTA)作为一种免疫检查点蛋白,可关键调节抗肿瘤作用
免疫力尽管取得了这一进展,但VISTA如何抑制T细胞活化尚不清楚。我们
目前的研究已经鉴定了一种新的VISTA相互作用受体,
人T细胞中,并介导VISTA的抑制作用。本项目的总体目标是
建议是定义这种新的T细胞共抑制的细胞和分子机制,
复杂.具体目标1将剖析VISTA与其受体之间的相互作用,并建立
泛素修饰酶与抑制信号的相关性。目标2将审查
VISTA及其受体在调节肿瘤特异性T细胞应答中的作用,利用新的
产生了条件性基因敲除小鼠和阻断这种抑制性受体的新型抑制剂
复杂. VISTA及其受体在人癌组织中的蛋白质表达水平也将
接受检查。总之,这些拟议的研究将建立一个基础,开发新的
靶向VISTA受体复合物的抑制剂用于癌症免疫疗法。
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)
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Li Lily Wang其他文献
Unraveling Immunogenomic Features Germane to Pathobiology of Myelodysplastic Syndromes
- DOI:
10.1182/blood-2024-198530 - 发表时间:
2024-11-05 - 期刊:
- 影响因子:
- 作者:
Arda Durmaz;Zachary Brady;Kartik Lakhotiya;Benjamin Kroger;Hussein Awada;Yasuo Kubota;Jacky Chen;Colin Hercus;Sébastien Hergalant;Carlos Bravo-Perez;Maria Teresa Voso;Li Lily Wang;Jacob G. Scott;Hetty E. Carraway;Valeria Visconte;Stephen Chung;Simona Pagliuca;Jaroslaw Maciejewski;Carmelo Gurnari - 通讯作者:
Carmelo Gurnari
Immune Checkpoint Molecules Regulate Paroxysmal Nocturnal Hemoglobinuria Clonal Evolution
- DOI:
10.1182/blood-2022-164937 - 发表时间:
2022-11-15 - 期刊:
- 影响因子:
- 作者:
Naomi Kawashima;BEN Ponvilawan;Pat Rayman;Jennifer Powers;Fauzia Ullah;Yasuo Kubota;Mai Aly;Li Lily Wang;Simona Pagliuca;Valeria Visconte;C. Marcela Diaz-Montero;Jaroslaw P. Maciejewski;Carmelo Gurnari - 通讯作者:
Carmelo Gurnari
Li Lily Wang的其他文献
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{{ truncateString('Li Lily Wang', 18)}}的其他基金
The Roles of a Novel Immune-Checkpoint Receptor Complex in Driving T Cell Dysfunction in Cancer
新型免疫检查点受体复合物在驱动癌症 T 细胞功能障碍中的作用
- 批准号:
10569043 - 财政年份:2022
- 资助金额:
$ 34.76万 - 项目类别:
The Roles of a Novel Immune-Checkpoint Receptor Complex in Driving T Cell Dysfunction in Cancer
新型免疫检查点受体复合物在驱动癌症 T 细胞功能障碍中的作用
- 批准号:
10435225 - 财政年份:2022
- 资助金额:
$ 34.76万 - 项目类别:
Transfer Application - R01 CA223804 - Chemoimmunoprevention of EGFR-Driven Non-Small Cell Lung Cancer
转移申请 - R01 CA223804 - EGFR 驱动的非小细胞肺癌的化学免疫预防
- 批准号:
10455258 - 财政年份:2018
- 资助金额:
$ 34.76万 - 项目类别:
VISTA, a novel checkpoint that suppresses anti-tumor T cell responses
VISTA,一种抑制抗肿瘤 T 细胞反应的新型检查点
- 批准号:
8880146 - 财政年份:2012
- 资助金额:
$ 34.76万 - 项目类别:
Vista, A Novel Checkpoint that Suppresses Anti-Tumor T Cell Responses
Vista,一种抑制抗肿瘤 T 细胞反应的新型检查点
- 批准号:
10424513 - 财政年份:2012
- 资助金额:
$ 34.76万 - 项目类别:
VISTA, a novel checkpoint that suppresses anti-tumor T cell responses
VISTA,一种抑制抗肿瘤 T 细胞反应的新型检查点
- 批准号:
9096775 - 财政年份:2012
- 资助金额:
$ 34.76万 - 项目类别:
VISTA, a novel checkpoint that suppresses anti-tumor T cell responses
VISTA,一种抑制抗肿瘤 T 细胞反应的新型检查点
- 批准号:
8531196 - 财政年份:2012
- 资助金额:
$ 34.76万 - 项目类别:
Vista, A Novel Checkpoint that Suppresses Anti-Tumor T Cell Responses
Vista,一种抑制抗肿瘤 T 细胞反应的新型检查点
- 批准号:
10634641 - 财政年份:2012
- 资助金额:
$ 34.76万 - 项目类别:
Vista, A Novel Checkpoint that Suppresses Anti-Tumor T Cell Responses
Vista,一种抑制抗肿瘤 T 细胞反应的新型检查点
- 批准号:
10207519 - 财政年份:2012
- 资助金额:
$ 34.76万 - 项目类别:
VISTA, a novel checkpoint that suppresses anti-tumor T cell responses
VISTA,一种抑制抗肿瘤 T 细胞反应的新型检查点
- 批准号:
8372583 - 财政年份:2012
- 资助金额:
$ 34.76万 - 项目类别:
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