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.
项目概要
使用离体扩增的抗肿瘤 T 细胞的过继细胞转移 (ACT) 引起了人们的极大兴趣,因为
在治疗黑色素瘤和其他癌症方面取得了成功。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难题
广泛应用基于 T 细胞的 ACT 疗法的主要障碍。目前淋巴细胞检测方法
富集导致杀肿瘤 T 细胞适度增加,而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着降低障碍(例如,降低成本、减少
脱靶效应)以促进 ACT 疗法的广泛传播。该项目的主要目标是开发一个
分离技术,根据杀肿瘤 T 细胞的能力来富集淋巴细胞群
识别自体肿瘤抗原。我们的微流控技术的前提是杀肿瘤T细胞可以
当暴露于肿瘤衍生肽主要组织相容性时,从大量白细胞群中分离出来
复合物 I 在最佳流动条件下。具体目标是: 1)开发微流控装置以丰富
具有抗原特异性 T 细胞的淋巴细胞群,以及 2) 展示微流体的能力
平台利用患者来源的外周血单核细胞富集杀肿瘤 T 细胞
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
为基于 T 细胞的 ACT 疗法的广泛应用以及不可知的特征(即没有先验)铺平了道路
需要肿瘤抗原的知识)该技术将使其广泛适用于
针对一系列癌症的个性化医疗方法。
项目成果
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