Analysis of Cell Sense Labeled Human Cells
Cell Sense 标记的人体细胞的分析
基本信息
- 批准号:7481330
- 负责人:
- 金额:$ 27.3万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-02-15 至 2009-08-14
- 项目状态:已结题
- 来源:
- 关键词:AdoptionAdoptive TransferAnimalsBiodistributionBiologicalCD34 geneCardiovascular DiseasesCell SurvivalCell TherapyCell TransplantationCell TransplantsCell divisionCellsCellular StructuresCharacteristicsClinicClinicalClinical TrialsCommittee MembersComplexConditionDendritic CellsDevelopmentDisabled PersonsDiseaseDoseEmulsionsEnsureFaceFederal GovernmentFluorineFluorocarbonsGoalsGovernmentGrantGuanosine MonophosphateHumanHuman bodyImageImaging technologyImmuneImmunotherapeutic agentIn VitroLabelLicensingMagnetic Resonance ImagingMalignant NeoplasmsMedicalMethodologyMonitorMusNatural Killer CellsNumbersOutcomePatternPhasePhenotypePhysiciansPopulationProceduresProductionProtocols documentationProtonsPublic HealthPurposeRangeReagentResearchResearch PersonnelRodent ModelSafetyScientistSmall Business Funding MechanismsSmall Business Innovation Research GrantSpecificityStem cellsSymptomsT-LymphocyteTechnologyTestingTherapeuticTherapeutic UsesTimeToxic effectTransplantationUniversitiesWorkcell motilitycell typecellular imagingclinically relevantcytotoxicityhandicapping conditionhuman diseasehuman subjectin vitro Assayin vivointerestmigrationnanoparticlenerve stem cellnervous system disordernoveloptimismperfluoropolyethertissue regenerationtrafficking
项目摘要
DESCRIPTION (provided by applicant): Cellular therapeutics represent great potential for curing and alleviating symptoms associated with debilitating human diseases, such as cancer, cardiovascular disease, and neurological disorders. Currently, no versatile methodology for tracking cellular products following administration exists, leading to delays in these therapies reaching the clinic. The ability to visualize the trafficking of transferred cells throughout the body non-invasively will give clinicians the ability to better understand why certain cellular transplants are successful and others are not. In addition, determining the biodistribution of transferred cells is of paramount importance to overcome government regulatory hurdles for these therapies. In this study, we propose characterizing a novel fluorochemical cell tracking reagent recently created for use with MRI, called Cell Sense. This product is an emulsion of fluorine-containing nanoparticles that is used to label cells in culture and enables transferred cells to be visualized with great specificity in vivo using 19F MRI. Cell Sense has been tested extensively in mouse cells and imaged using in vivo rodent models. It has not yet been tested on clinically relevant human cells. In this proposal, we will examine the Cell Sense labeling characteristics in a variety of primary human immune cell types, including dendritic cells, natural killer cells, and T cells, that are currently being used in immunotherapeutic trials. Also, stem cells, including human neural progenitor cells (hNPC) and CD34+ cell types, will be studied. This proposal has two Specific Aims: (1) to develop ex vivo cell labeling protocols and examine the Cell Sense labeling dose in therapeutically relevant human cells; and (2) to determine whether the fluorochemical labeling has any detrimental impact on human cell viability or normal function. To achieve these Aims, we will employ an extensive battery of in vitro assays to assess cell loading, cytotoxicity, proliferation, phenotype, and function. Combining these results, we will be able to devise optimal labeling protocols for a diverse range of cell types that are currently being used for human clinical trials. By establishing Cell Sense's ability to label a wide variety of human cells with limited toxicity, we will have achieved a critical milestone in moving closer toward a clinical-grade product that can be used to track current transplanted cells for therapeutic use. We believe that the potential impact of Cell Sense is significant, by removing many of the scientific and regulatory hurdles that developers of cellular therapeutics for the clinic currently face. PUBLIC HEALTH RELEVANCE: Understanding how therapeutically relevant cell types behave following adoptive transfer or transplantation may help us develop novel therapies. This project examines the use of novel fluorochemical MRI reagents to image and detect labeled, transplanted cells non-invasively. The results of this study will move MRI cell tracking closer to clinical adoption and will provide researchers and physicians the opportunity to selectively follow labeled cells following administration.
描述(由申请人提供):细胞疗法在治愈和缓解与衰弱的人类疾病相关的症状方面具有巨大的潜力,如癌症、心血管疾病和神经疾病。目前,没有通用的方法来跟踪服用后的细胞产品,导致这些疗法延迟进入临床。能够非侵入性地可视化转移细胞在体内的运输,将使临床医生能够更好地理解为什么某些细胞移植成功,而另一些则不成功。此外,确定转移细胞的生物分布对于克服政府对这些疗法的监管障碍至关重要。在这项研究中,我们建议表征一种最近创建的用于MRI的新型荧光化学细胞跟踪试剂,称为Cell Sense。该产品是一种含氟纳米颗粒的乳剂,用于标记培养中的细胞,并使转移的细胞能够使用19F MRI在体内以极高的特异性可视化。细胞感觉已经在小鼠细胞中进行了广泛的测试,并使用活体啮齿动物模型进行了成像。它还没有在临床相关的人类细胞上进行测试。在这项提案中,我们将检查目前用于免疫治疗试验的各种原始人类免疫细胞类型的细胞正义标记特征,包括树突状细胞、自然杀伤细胞和T细胞。此外,还将研究干细胞,包括人类神经前体细胞(HNPC)和CD34+细胞类型。这项建议有两个具体目标:(1)制定体外细胞标记方案,并检查与治疗相关的人体细胞中的细胞正义标记剂量;(2)确定荧光化学标记是否对人类细胞活性或正常功能有任何有害影响。为了实现这些目标,我们将使用广泛的体外测试来评估细胞负载、细胞毒性、增殖、表型和功能。结合这些结果,我们将能够为目前用于人体临床试验的各种细胞类型设计出最佳的标记方案。通过建立Cell Sense标记毒性有限的多种人类细胞的能力,我们将在迈向临床级产品方面实现一个关键里程碑,该产品可用于跟踪当前用于治疗用途的移植细胞。我们认为,通过消除临床细胞疗法开发商目前面临的许多科学和监管障碍,Cell Sense的潜在影响是显著的。公共卫生相关性:了解与治疗相关的细胞类型在收养转移或移植后的表现,可能有助于我们开发新的治疗方法。本项目研究使用新型荧光化学核磁共振试剂对标记的移植细胞进行非侵入性成像和检测。这项研究的结果将使MRI细胞跟踪更接近临床应用,并将为研究人员和医生提供在给药后有选择地跟踪标记细胞的机会。
项目成果
期刊论文数量(0)
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Robbie B Mailliard其他文献
Naive CD8+ T cells from ART respond to primary vaccination against autologous HIV-1 antigen
- DOI:
10.1186/1742-4690-9-s1-p16 - 发表时间:
2012-05-25 - 期刊:
- 影响因子:3.900
- 作者:
Kellie N Smith;Robbie B Mailliard;Weimin Jiang - 通讯作者:
Weimin Jiang
Robbie B Mailliard的其他文献
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{{ truncateString('Robbie B Mailliard', 18)}}的其他基金
Immune response to COVID-19 vaccine in HIV infected men and women
HIV 感染男性和女性对 COVID-19 疫苗的免疫反应
- 批准号:
10686994 - 财政年份:2021
- 资助金额:
$ 27.3万 - 项目类别:
Immune response to COVID-19 vaccine in HIV infected men and women
HIV 感染男性和女性对 COVID-19 疫苗的免疫反应
- 批准号:
10402431 - 财政年份:2021
- 资助金额:
$ 27.3万 - 项目类别:
Immune response to COVID-19 vaccine in HIV infected men and women
HIV 感染男性和女性对 COVID-19 疫苗的免疫反应
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10494217 - 财政年份:2021
- 资助金额:
$ 27.3万 - 项目类别:
Programming Dendritic Cells to Expose the Persistent HIV-1 Latent Reservoir for Immune Targeting
对树突状细胞进行编程以暴露持久的 HIV-1 潜伏库以实现免疫靶向
- 批准号:
9347740 - 财政年份:2017
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