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：
Venktesh Shirure
金额：
$ 21.66万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
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：
https://reporter.nih.gov/project-details/10613173
关键词：
Acceleration Adoptive Cell Transfers Affinity Autologous Autologous Tumor Cell Biomedical Engineering Blood Blood Cells CD8-Positive T-Lymphocytes Cancer Patient Cell Adhesion Cell Density Cell Fraction Cell Line Cell Separation Cells Cellular immunotherapy Clinical Clinical Oncology Collaborations Device Designs Devices Dimensions Exposure to Goals Heterogeneity Immunology Interferon Type II Knowledge Leukocytes Lymphocyte MART-1 Tumor Antigen Major Histocompatibility Complex Malignant Neoplasms Melanoma Cell Methods Microfluidic Microchips Microfluidics Molecular Patients Peptides Perfusion Peripheral Blood Lymphocyte Peripheral Blood Mononuclear Cell Population Preparation Process Publishing Research Personnel Sampling Source Surface Surgical Oncology T cell receptor repertoire sequencing T cell therapy T-Lymphocyte Technology Tumor Antigens Tumor-Derived Tumor-Infiltrating Lymphocytes anticancer research antigen-specific T cells cancer cell cancer immunotherapy cost improved outcome interest melanoma microfluidic technology neoplastic cell new technology novel therapeutic intervention peripheral blood personalized medicine programs statistics success technology development tumor

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。