Increasing Thiols for Improving T cell Immunotherapy
Increasing Thiols for Improving T cell Immunotherapy
批准号:
10603006
负责人:
Shikhar Mehrotra
金额:
$39.42万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
已结题
起止时间:
2022-09-13 至 2024-08-31
关键词:
Adoptive Cell TransfersAdoptive TransferAntigensAntioxidantsBiological MarkersCancer PatientCell DeathCell surfaceCellsChronicDataEffectivenessEnsureEpitopesExhibitsFRAP1 geneGenerationsGlycolysisHumanHuman EngineeringImmunosuppressionImmunotherapyLegal patentMalignant NeoplasmsMeasuresMediatingMembrane PotentialsMemoryMetabolicMetabolismMethodsOxidation-ReductionOxidative PhosphorylationPathway interactionsPatientsPhase I Clinical TrialsPhenotypePlayPopulationPredispositionPropertyProstateProtocols documentationRecombinantsRecurrenceResearchRetroviral VectorRoleSignaling MoleculeSolid NeoplasmStandardizationStressSulfhydryl CompoundsT cell responseT cell therapyT memory cellT-LymphocyteTXN geneTranscription Factor AP-1Transgenic MiceTranslatingTranslationsTreatment EfficacyTumor ImmunityTumor-DerivedTumor-Infiltrating LymphocytesXenograft Modelcommercializationcostexperimental studyglucose uptakeimprovedin vivoin vivo Modelinnovationinnovative technologiesmitochondrial membranemitochondrial metabolismneoplastic celloverexpressionpreservationprogramsstem-like cellsubcutaneoustumortumor growthtumor microenvironment
中文摘要
摘要
英文摘要
ABSTRACT
New strategies to improve adoptive cell therapy (ACT) protocols are emerging to enhance in vivo persistence of
adoptively transferred tumor epitope-specific T cells and overcome tumor-induced immunosuppression. Our
preliminary data suggests that there is a direct correlation between the long-lived central memory T cells (Tcm)
and their anti-oxidant capacity. Overexpression of thioredoxin-1 (Trx), a critical molecule that regulates cell-
surface thiols (c-SH), increased Tcm phenotype in T cells obtained from TCR transgenic mouse crossbred with
Trx transgenic mouse, or engineering human T cells with a retroviral vector with TCR and Trx together. These
preliminary observations led us to hypothesize that “the presence of Trx drives tumor-reactive T cells to a c-SHhi
phenotype, which results in increased persistence in the oxidative tumor microenvironment and improved tumor
control." We propose to further strengthen the translational aspect of this strategy by determining if strategies to
increase anti-oxidant capacity in presence of recombinant thioredoxin (rTrx) can reprogram tumor-infiltrating
lymphocytes and improve TIL-mediated ACT. The experiments are planned under the following specific aims: 1)
To determine if human tumor-derived TILs could be ex vivo programmed with rTRx and exhibit enhanced anti-
tumor phenotype, 2) To establish if rTrx TILs are superior to conventional TILs in controlling tumor growth in
vivo. We believe that our studies are innovative and will uncover essential aspects that need to be considered
when generating tumor-specific Tcm/Tscm cells for the ACT and enhance its wider use by decreasing the
prohibitive costs.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Intersections of RNA-binding proteins and T-cells in oral epithelial plasticity
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批准号:10417171
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项目类别:
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资助金额:$45.19万
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财政年份:2020
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负责人:Shikhar Mehrotra
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依托单位:
Understanding Metabolic and Epigenetic Cross‐ talk in Potent Anti‐ tumor T cells
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批准号:10400117
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项目类别:
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资助金额:$45.45万
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财政年份:2020
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负责人:Shikhar Mehrotra
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依托单位:
Intersections of RNA-binding proteins and T-cells in oral epithelial plasticity
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批准号:10178000
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项目类别:
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资助金额:$45.49万
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财政年份:2020
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负责人:Shikhar Mehrotra
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依托单位:
Programming Metabolically Fit TILs for Immunotherapy
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批准号:9906726
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项目类别:
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资助金额:$22.46万
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财政年份:2020
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负责人:Shikhar Mehrotra
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依托单位:
Understanding Metabolic and Epigenetic Cross‐ talk in Potent Anti‐ tumor T cells
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批准号:10599308
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项目类别:
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资助金额:$45.45万
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财政年份:2020
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负责人:Shikhar Mehrotra
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依托单位:
Understanding Metabolic and Epigenetic Cross‐ talk in Potent Anti‐ tumor T cells
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批准号:10163144
-
项目类别:
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资助金额:$46.37万
-
财政年份:2020
-
负责人:Shikhar Mehrotra
-
依托单位:
Intersections of RNA-binding proteins and T-cells in oral epithelial plasticity
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批准号:10632129
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项目类别:
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资助金额:$0.34万
-
财政年份:2020
-
负责人:Shikhar Mehrotra
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依托单位:
Programming Metabolically Fit TILs for Immunotherapy
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批准号:10822377
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项目类别:
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资助金额:$100.0万
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财政年份:2020
-
负责人:Shikhar Mehrotra
-
依托单位:
Anti-oxidant and Metabolic Phenotype in Regulating Tumor Specific T cell Memory Response
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批准号:10300448
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项目类别:
-
资助金额:$50.12万
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财政年份:2019
-
负责人:Shikhar Mehrotra
-
依托单位:
Anti-oxidant and Metabolic Phenotype in Regulating Tumor Specific T cell Memory Response
-
批准号:9917102
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项目类别:
-
资助金额:$52.24万
-
财政年份:2019
-
负责人:Shikhar Mehrotra
-
依托单位:
Anti-oxidant and Metabolic Phenotype in Regulating Tumor Specific T cell Memory Response
-
批准号:10055964
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项目类别:
-
资助金额:$51.11万
-
财政年份:2019
-
负责人:Shikhar Mehrotra
-
依托单位:
Anti-oxidant and Metabolic Phenotype in Regulating Tumor Specific T cell Memory Response
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批准号:10531896
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项目类别:
-
资助金额:$50.12万
-
财政年份:2019
-
负责人:Shikhar Mehrotra
-
依托单位:
Core B: Animal Models and Pathology
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批准号:9072010
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项目类别:
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资助金额:$22.05万
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财政年份:2016
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负责人:Shikhar Mehrotra
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依托单位:
Mouse Core
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批准号:8555365
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项目类别:
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资助金额:$29.5万
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财政年份:2011
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负责人:Shikhar Mehrotra
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依托单位:
Impact of AICD on TCR Transduced T Cells for Adoptive Immunotherapy
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批准号:8555359
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项目类别:
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资助金额:$28.43万
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财政年份:2011
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负责人:Shikhar Mehrotra
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依托单位:
Oxidative stress and AICD in memory T cell persistence
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批准号:8461917
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项目类别:
-
资助金额:$27.91万
-
财政年份:2010
-
负责人:Shikhar Mehrotra
-
依托单位:
Oxidative stress and AICD in memory T cell persistence
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批准号:8249469
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项目类别:
-
资助金额:$29.69万
-
财政年份:2010
-
负责人:Shikhar Mehrotra
-
依托单位:
Oxidative stress and AICD in memory T cell persistence
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批准号:8658396
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项目类别:
-
资助金额:$28.8万
-
财政年份:2010
-
负责人:Shikhar Mehrotra
-
依托单位:
Oxidative stress and AICD in memory T cell persistence
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批准号:8080270
-
项目类别:
-
资助金额:$29.69万
-
财政年份:2010
-
负责人:Shikhar Mehrotra
-
依托单位:
Oxidative stress and AICD in memory T cell persistence
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批准号:7987679
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项目类别:
-
资助金额:$30.61万
-
财政年份:2010
-
负责人:Shikhar Mehrotra
-
依托单位:
海外基金