Nanoparticles to Track T Cell Immunotherapy Using Magnetic Particle Imaging
使用磁粒子成像追踪 T 细胞免疫治疗的纳米粒子
基本信息
- 批准号:10365339
- 负责人:
- 金额:$ 47.21万
- 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
- 起止时间:2022-05-15 至 2026-01-31
- 项目状态:未结题
- 来源:
- 关键词:Adoptive Cell TransfersAffectAnimalsAnisotropyBenchmarkingBiodistributionBiological AssayBiomedical EngineeringBlood Circulation TimeCaliberCancer ModelCell CountCell SurvivalCellsChargeCoculture TechniquesComputer ModelsCoupledCytotoxic T-LymphocytesDefectDiseaseDoseElectron MicroscopyEnvironmentEuthanasiaExocytosisFailureFlow CytometryFluorescence MicroscopyFoundationsFutureGenerationsGlioblastomaGliomaGoalsImageImaging technologyImmunotherapyImpact evaluationIn VitroIntracranial NeoplasmsIonizing radiationLabelLifeLongitudinal StudiesMagnetic Resonance ImagingMagnetic nanoparticlesMagnetismMalignant NeoplasmsMeasuresMediatingMethodsModelingModificationMolecularMonitorMotivationMultimodal ImagingMusOrganOxygenPenetrationPerformancePhenotypePhysicsPolymersPreclinical TestingPropertyQuantitative EvaluationsResearchResearch Project GrantsResolutionRouteSignal TransductionSiteSolidSolid NeoplasmSpecificityStratificationSurfaceT cell therapyT-LymphocyteTherapeuticTissuesToxic effectTracerValidationWorkbiomaterial developmentcancer cellcancer immunotherapycancer therapyclinical translationcytotoxicimaging approachimaging modalityimmune imagingimprovedin vivoinsightinstrumentationinterestiron oxide nanoparticlemagnetic fieldmelanomamolecular imagingmouse modelnanoparticleneoplastic cellnuclear imagingparticlepreclinical evaluationpublic health relevancequantitative imagingresearch and developmentresponders and non-respondersresponsesuccesssuperparamagnetismtomographytooltraffickingtreatment responsetumoruptake
项目摘要
Project Summary
A critical step in the success of adoptive cell transfer (ACT) T cell immunotherapy in solid cancers is achieving
trafficking and persistence of T cells at tumor sites, while avoiding toxicities due to T cell attack of off-target
tissues and organs. Non-invasive quantitative imaging would be a powerful tool to understand mechanisms of
action and failure of T cell immunotherapies, evaluate the impact of T cell modifications and delivery routes,
monitor off-target T cell accumulation, and stratify response to therapy on the basis of measures of T cell tumor
accumulation. This Bioengineering Research Grant project will pioneer non-invasive and quantitative tracking of
adoptive T cell cancer immunotherapy using magnetic particle imaging (MPI), a new molecular imaging modality
that enables non-invasive, unambiguous, and tomographic analysis of the whole-body distribution of
superparamagnetic iron oxide nanoparticles (SPIONs). Preliminary results demonstrate non-invasive
quantitative tracking of ACT T cells in solid intracranial tumors, synthesis of tracers with enhanced MPI sensitivity,
and current sensitivity of 5x103 T cells. The proposed work aims to improve sensitivity to 5x102 T cells and
demonstrate the accuracy of MPI in quantifying T cell biodistribution in mouse models of cancer. Modeling of
MPI physics by the PI demonstrates that tracers optimal for MPI must have uniform physical and magnetic
properties and low magnetocrystalline anisotropy, to enable fast dipole switching at large SPION diameters. The
PI has developed a new synthesis that yields defect-free SPIONs with uniform magnetic properties and low
magnetocrystalline anisotropy. The proposed work (Aim 1) will couple this new synthesis with modeling of MPI
physics and comprehensive physical and magnetic characterization to gain fundamental understanding of the
relation between SPION properties and MPI performance and to obtain SPIONs with superior sensitivity. Imaging
approaches to track T cells must not compromise their viability or function and T cells pose unique challenges
for nanoparticle labeling. The proposed work (Aim 2) will define an upper limit for labeling primary T cells with
MPI tracers without compromising viability or function using tracers that associate with T cells through charge
interactions. Preliminary studies demonstrate non-invasive tracking of T cell biodistribution in mice using MPI,
and that SPION-labeled T cells reach solid tumors after systemic administration in murine models. The proposed
work (Aim 3) will validate in vivo tracking of ACT T cell therapy using MPI against T cell counting using flow
cytometry and will evaluate dynamics of T cell accumulation in tumors longitudinally using MPI. The proposed
biomaterials-development research plan is enabled by the complementary expertise of the PI (SPIONs and MPI
physics) and Co-I (ACT T cell therapies) and access to state-of-the-art instrumentation to characterize SPION
MPI performance ex vivo and in vivo. Achieving the target sensitivity of 5x102 T cells will provide an order-of-
magnitude improvement in quantitative cell tracking sensitivity over other whole body quantitative imaging
technologies, establishing MPI as a powerful tool in the immunoimaging toolbox.
项目总结
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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Carlos M Rinaldi-Ramos其他文献
Carlos M Rinaldi-Ramos的其他文献
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{{ truncateString('Carlos M Rinaldi-Ramos', 18)}}的其他基金
NIH Administrative Supplement to Promote Diversity in Health Related Research
NIH 促进健康相关研究多样性的行政补充
- 批准号:
10876754 - 财政年份:2023
- 资助金额:
$ 47.21万 - 项目类别:
Nanoparticles for In Vivo Labeling of T Cells During Cancer Immunotherapy
用于癌症免疫治疗期间 T 细胞体内标记的纳米颗粒
- 批准号:
10450938 - 财政年份:2022
- 资助金额:
$ 47.21万 - 项目类别:
Nanoparticles for In Vivo Labeling of T Cells During Cancer Immunotherapy
用于癌症免疫治疗期间 T 细胞体内标记的纳米颗粒
- 批准号:
10634620 - 财政年份:2022
- 资助金额:
$ 47.21万 - 项目类别:
Nanoparticles to Track T Cell Immunotherapy Using Magnetic Particle Imaging
使用磁粒子成像追踪 T 细胞免疫治疗的纳米粒子
- 批准号:
10621153 - 财政年份:2022
- 资助金额:
$ 47.21万 - 项目类别:
Innovative Non-Invasive Imaging of Traumatic Brain Injury
创伤性脑损伤的创新非侵入性成像
- 批准号:
10527640 - 财政年份:2022
- 资助金额:
$ 47.21万 - 项目类别:
Magnetically Templated Regeneration Scaffolds for Nerve Injury Repair
用于神经损伤修复的磁模板再生支架
- 批准号:
8954155 - 财政年份:2015
- 资助金额:
$ 47.21万 - 项目类别:
Modeling of the Magnetic Particle Imaging Signal Due to Magnetic Nanoparticles
磁性纳米粒子产生的磁性粒子成像信号的建模
- 批准号:
9024525 - 财政年份:2015
- 资助金额:
$ 47.21万 - 项目类别:
Magnetically Templated Regeneration Scaffolds for Nerve Injury Repair
用于神经损伤修复的磁模板再生支架
- 批准号:
9086452 - 财政年份:2015
- 资助金额:
$ 47.21万 - 项目类别:
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