Project 1: Targeting the Neutrophil Lineage To Enhance Immune Checkpoint Inhibitor Efficacy in NSCLC
Project 1: Targeting the Neutrophil Lineage To Enhance Immune Checkpoint Inhibitor Efficacy in NSCLC
批准号:
10174872
负责人:
A McGarry Houghton
金额:
$26.33万
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-08-01 至 2022-03-31
关键词:
AccountingAddressAntibody TherapyAntigensAtypical lymphocyteBiopsy SpecimenCD8-Positive T-LymphocytesCD8B1 geneCancer EtiologyCancer PatientCell LineageCellsCessation of lifeClinicalClinical TrialsConsentCore BiopsyCorrelative StudyDataData SetDevelopmentFailureFred Hutchinson Cancer Research CenterGene Expression ProfileGenetically Engineered MouseGoalsHumanIL8RA geneIL8RB geneImmuneImmune checkpoint inhibitorImmune responseImmune systemImmunohistochemistryImmunotherapeutic agentImmunotherapyInterferon Type IILungLung AdenocarcinomaMalignant - descriptorMalignant NeoplasmsMalignant neoplasm of lungModelingMolecular GeneticsMusMutant Strains MiceMutationMyelogenousMyeloid CellsNivolumabNon-Small-Cell Lung CarcinomaOutcomePD-1/PD-L1PatientsPhase II Clinical TrialsPhenotypePopulationPre-Clinical ModelProspective cohortRetrospective cohortSafetySingle Nucleotide PolymorphismSlideSmokeSolid NeoplasmSpecimenTestingTherapeuticTissuesTreatment EfficacyTreatment FailureWorkanti-PD-1anti-PD-L1 antibodiesanti-PD-L1 therapyanti-PD1 antibodiesanti-PD1 therapybasecancer typecell typecheckpoint therapycigarette smokecigarette smokingco-clinical trialcohortdesignexhaustexhaustionimmune checkpointimmune checkpoint blockadeimprovedmortalitymouse modelnano-stringneutrophilnovelnovel diagnosticsnovel therapeuticspreventprospectiveresponsesmall moleculesuccesstreatment responsetumortumor microenvironment
中文摘要
项目摘要/摘要-项目1
英文摘要
Project Summary/Abstract – Project 1
Although immune checkpoint inhibitor (ICI) therapy has been a tremendous clinical success, just ~20% of non-
small cell lung cancer (NSCLC) patients respond to anti-PD1/PDL1 therapy. In efforts to improve upon this
figure, the field has launched over 800 clinical trials (across all cancer types) testing novel therapeutics in
conjunction with immune checkpoint blockade. Effectively none of these trials adequately address the
neutrophil lineage as a substantial contributor to ICI treatment failure. We provide preliminary data that
neutrophils are the most prevalent immune cell type in NSCLC, inversely correlate with CD8 cellular content,
and preclude the presence of the IFNγ signature, previously shown to correlate with favorable ICI treatment
response. We will perform multiplex-immunohistochemistry on a dataset of FFPE slides obtained from patients
treated with anti-PD1/PDL1 therapy to show that neutrophils associate with poor outcomes. We utilize a novel
mouse model in which the tumor harbors hundreds of mutations to identify the mechanistic determinants of ICI
treatment response and test a novel CXCR1/CXCR2 antagonist to synergize with anti-PDL1 treatment. Lastly,
we will perform a Phase 2 clinical trial testing the combination of the novel CXCR1/CXCR2 antagonist (SX-682,
Syntrix Biosystems, Inc.) and nivolumab in advanced stage NSCLC patients who have previously failed anti-
PD1/PDL1 therapy.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Neutrophil derived proteinases abolish the IFNG signature in NSCLC
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批准号:10717448
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项目类别:
-
资助金额:$57.31万
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财政年份:2023
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负责人:A McGarry Houghton
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依托单位:
Anxa2 drives the function of immune suppressive neutrophils in lung cancer
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批准号:10310981
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项目类别:
-
资助金额:$4.02万
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财政年份:2021
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负责人:A McGarry Houghton
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依托单位:
A Quantitative PET/CT Research Resource for Co-Clinical Imaging of Lung Cancer Therapies
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批准号:10301566
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项目类别:
-
资助金额:$66.03万
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财政年份:2021
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负责人:A McGarry Houghton
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依托单位:
A Quantitative PET/CT Research Resource for Co-Clinical Imaging of Lung Cancer Therapies
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批准号:10700944
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项目类别:
-
资助金额:$38.98万
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财政年份:2021
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负责人:A McGarry Houghton
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依托单位:
Liquid biopsy of the lung to profile lung cancer
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批准号:10053675
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项目类别:
-
资助金额:$42.79万
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财政年份:2020
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负责人:A McGarry Houghton
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依托单位:
Liquid biopsy of the lung to profile lung cancer
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批准号:10259860
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项目类别:
-
资助金额:$25.9万
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财政年份:2020
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负责人:A McGarry Houghton
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依托单位:
Liquid biopsy of the lung to profile lung cancer
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批准号:10472743
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项目类别:
-
资助金额:$38.97万
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财政年份:2020
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负责人:A McGarry Houghton
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依托单位:
Liquid biopsy of the lung to profile lung cancer
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批准号:10601449
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项目类别:
-
资助金额:$14.31万
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财政年份:2020
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负责人:A McGarry Houghton
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依托单位:
Administrative Core
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批准号:10174875
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项目类别:
-
资助金额:$17.39万
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财政年份:2019
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负责人:A McGarry Houghton
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依托单位:
Administrative Core
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批准号:10601298
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项目类别:
-
资助金额:$5.45万
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财政年份:2019
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负责人:A McGarry Houghton
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依托单位:
Developmental Research Program
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批准号:10700903
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项目类别:
-
资助金额:$8.18万
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财政年份:2019
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负责人:A McGarry Houghton
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依托单位:
Administrative Core
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批准号:10700915
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项目类别:
-
资助金额:$22.85万
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财政年份:2019
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负责人:A McGarry Houghton
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依托单位:
Tumor-specific autoantibodies for SCLC early detection
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批准号:10299616
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项目类别:
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资助金额:$14.89万
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财政年份:2019
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负责人:A McGarry Houghton
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依托单位:
Fred Hutchinson Cancer Research Center Lung SPORE
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批准号:10174865
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项目类别:
-
资助金额:$186.35万
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财政年份:2019
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负责人:A McGarry Houghton
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依托单位:
Tumor-specific autoantibodies for SCLC early detection
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批准号:9912430
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项目类别:
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资助金额:$57.33万
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财政年份:2019
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负责人:A McGarry Houghton
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依托单位:
Tumor-specific autoantibodies for SCLC early detection
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批准号:10601432
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项目类别:
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资助金额:$27.38万
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财政年份:2019
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负责人:A McGarry Houghton
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依托单位:
Fred Hutchinson Cancer Research Center Lung SPORE
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批准号:10601288
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项目类别:
-
资助金额:$58.18万
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财政年份:2019
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负责人:A McGarry Houghton
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依托单位:
Project 1: Targeting the Neutrophil Lineage To Enhance Immune Checkpoint Inhibitor Efficacy in NSCLC
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批准号:10700909
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项目类别:
-
资助金额:$34.64万
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财政年份:2019
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负责人:A McGarry Houghton
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依托单位:
Developmental Research Program
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批准号:10601290
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项目类别:
-
资助金额:$1.96万
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财政年份:2019
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负责人:A McGarry Houghton
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依托单位:
Developmental Research Program
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批准号:10174868
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项目类别:
-
资助金额:$6.22万
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财政年份:2019
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负责人:A McGarry Houghton
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依托单位:
海外基金