Microfluidic technology to isolate tumoricidal T-cells from peripheral blood
微流控技术从外周血中分离杀肿瘤T细胞
基本信息
- 批准号:10613173
- 负责人:
- 金额:$ 21.66万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-01 至 2026-07-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAdoptive Cell TransfersAffinityAutologousAutologous Tumor CellBiomedical EngineeringBloodBlood CellsCD8-Positive T-LymphocytesCancer PatientCell AdhesionCell DensityCell FractionCell LineCell SeparationCellsCellular immunotherapyClinicalClinical OncologyCollaborationsDevice DesignsDevicesDimensionsExposure toGoalsHeterogeneityImmunologyInterferon Type IIKnowledgeLeukocytesLymphocyteMART-1 Tumor AntigenMajor Histocompatibility ComplexMalignant NeoplasmsMelanoma CellMethodsMicrofluidic MicrochipsMicrofluidicsMolecularPatientsPeptidesPerfusionPeripheral Blood LymphocytePeripheral Blood Mononuclear CellPopulationPreparationProcessPublishingResearch PersonnelSamplingSourceSurfaceSurgical OncologyT cell receptor repertoire sequencingT cell therapyT-LymphocyteTechnologyTumor AntigensTumor-DerivedTumor-Infiltrating Lymphocytesanticancer researchantigen-specific T cellscancer cellcancer immunotherapycostimproved outcomeinterestmelanomamicrofluidic technologyneoplastic cellnew technologynovel therapeutic interventionperipheral bloodpersonalized medicineprogramsstatisticssuccesstechnology developmenttumor
项目摘要
PROJECT SUMMARY
Adoptive cell transfer (ACT) using ex vivo expanded anti-tumor T-cells has garnered significant interest due to
successes in treating melanoma and other cancers. This is a highly personalized therapy, in which autologous
T-cells that can target the tumors are required. However, finding cells that specifically target tumors remains a
major hurdle for the widespread application of T-cell based ACT therapies. The current methods of lymphocyte
enrichment result in modest increases in tumoricidal T-cells with little control over the clonal heterogeneity. A
technology that overcomes these challenges would significantly lower the barriers (e.g., reduce cost, reduce
off-target effects) for broad dissemination of ACT therapies. The primary goal of this project is to develop a
separation technology to enrich a population of lymphocytes with tumoricidal T-cells based on their capacity to
recognize autologous tumor antigens. The premise of our microfluidic technology is that tumoricidal T-cells can
be separated from a bulk leukocyte population when exposed to tumor-derived peptide-major histocompatibility
complex I under optimal flow conditions. The specific aims are to: 1) Develop a microfluidic device to enrich a
population of lymphocytes with antigen specific T-cells, and 2) Demonstrate the capacity of the microfluidic
platform to enrich patient-derived Peripheral Blood Mononuclear Cells with tumoricidal T-cells using patient-
matched tumor cells. Accomplishing our primary goal will create a potentially disruptive technology that could
pave way for wide-spread application of T-cell based ACT therapies, and the agnostic feature (i.e., no a priori
knowledge of tumor antigen(s) is required) of the technology would make it broadly applicable for a
personalized medicine approach to a range of cancers.
项目总结
使用体外扩增的抗肿瘤T细胞进行过继细胞转移(ACT)已引起人们的极大兴趣,因为
在治疗黑色素瘤和其他癌症方面取得成功。这是一种高度个性化的疗法,其中自体
需要能够靶向肿瘤的T细胞。然而,寻找特异性靶向肿瘤的细胞仍然是一个
以T细胞为基础的ACT疗法广泛应用的主要障碍。淋巴细胞的现行检测方法
浓缩会导致杀瘤T细胞的适度增加,但对克隆异质性几乎没有控制。一个
克服这些挑战的技术将显著降低障碍(例如,降低成本、减少
非目标效应),以广泛传播ACT疗法。这个项目的主要目标是开发一种
基于杀伤T细胞的能力来丰富淋巴细胞群体的分离技术
识别自体肿瘤抗原。我们的微流控技术的前提是杀瘤T细胞可以
当暴露于肿瘤衍生的主要组织相容性时,从大量白细胞群中分离出来
最优流动条件下的复合体I。具体目的是:1)开发一种微流控装置,以富集
具有抗原特异性T细胞的淋巴细胞群体,以及2)展示微流控的能力
利用患者-抗肿瘤T细胞丰富患者外周血单个核细胞的平台
匹配的肿瘤细胞。实现我们的主要目标将创造一种潜在的颠覆性技术,可能
为T细胞为基础的ACT疗法的广泛应用铺平道路,以及不可知的特征(即,没有先验
该技术的肿瘤抗原知识(需要S)将使其广泛适用于
针对一系列癌症的个性化医疗方法。
项目成果
期刊论文数量(0)
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Venktesh Shirure其他文献
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