| 项目编号: | 1645229
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| 项目名称: | EAGER: Biomanufacturing: Towards Reproducible and Scalable Biomanufacturing of Tumor-Specific T Cells with Optimal Phenotype and Function for Personalized Immunotherapy |
| 作者: | Fei Wen
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| 承担单位: | University of Michigan Ann Arbor
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| 批准年: | 2016
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| 开始日期: | 2016-09-01
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| 结束日期: | 2018-08-31
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| 资助金额: | 300000
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| 资助来源: | US-NSF
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| 项目类别: | Standard Grant
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| 国家: | US
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| 语种: | 英语
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| 特色学科分类: | Engineering - Chemical, Bioengineering, Environmental, and Transport Systems
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| 英文关键词: | t cell
; t-cell
; t-cell profiling method
; manufacturing process
; act
; personalized cancer immunotherapy
; biomanufacturing
; function
; anti-tumor
; heterogeneous population
; phenotype
; different stage
; patient-to-patient variability
; valuable opportunity
; high anti-tumor activity
; optimal expansion condition
; effective adoptive t-cell therapy
; quality control protocol
; adoptive t-cell therapy
; large-scale manufacturing
; subdominant tumor-associated antigen
; different type
; objective data-analysis automation
; multiple roadblock
; visualization method
; current standard technology
; anti-tumor activity
; public scientific literacy
; power engineering outreach endeavor
; innovative pedagogy
; high-dimensional datum
; fundamental knowledge
; different approach
; quality control step
; molecular metric
; simultaneous detection
; k-12 student
; significant benefit
; transformative potential
; such metric
; therapeutic effectiveness
; graduate curricula
; significant technical challenge
; breast cancer
; innovative artificial antigen presentation system
; significant challenge
; therapeutic purpose
; new generation
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| 英文摘要: | 1645229 - Wen
Cancer is responsible for about 25% of deaths in the US. Developing an effective adoptive T-cell therapy (ACT), a promising and highly personalized cancer immunotherapy, holds significant benefits for society. However, it remains a significant challenge to develop reproducible and scalable manufacturing processes to reliably generate T cells with high anti-tumor activity. This project aims to address this challenge by developing a rapid, simple, and comprehensive T-cell profiling method. It represents a novel and radically different approach with transformative potential by addressing multiple roadblocks to the commercialization of ACT, including manufacturing reproducibility, therapeutic effectiveness and patient-to-patient variability. Research findings will also be used to strengthen undergraduate and graduate curricula, to power engineering outreach endeavors that encourage early exposure of K-12 students to science and engineering, and to increase public scientific literacy. Innovative pedagogies will be developed that can be readily incorporated by educators at all levels to improve their students' learning. These efforts will collectively help create a new generation of engineers with skills and fundamental knowledge in both engineering and life sciences.
Adoptive T-cell therapy (ACT) is a highly personalized cancer immunotherapy that involves the infusion into patients of their natural or genetically engineered tumor-reactive T cells manufactured ex vivo. Expansion of a single naïve human T cell yields a heterogeneous population exhibiting a range of phenotype and function. While this diversity helps T cells acquire specialized responses to different types of pathogens and cancers at different stages, it represents a significant technical challenge to reproducible, large-scale manufacturing of T cells for therapeutic purposes. Therefore, it is critical to have a high performance T-cell profiling method to closely monitor their phenotype, function and specificity. Unfortunately, the current standard technology requires several sample runs, adding complexity, variability and workload to the manufacturing process. To address this issue, a T-cell profiling method will be developed to enable simultaneous detection of dozens of parameters on single T cells in a heterogeneous population in a single run. Visualization methods of the resulting high-dimensional data will be developed to facilitate objective data-analysis automation in the quality control steps of the manufacturing process. In parallel, by developing and applying an innovative artificial antigen presentation system, T cells specific to a range of subdominant tumor-associated antigens found in breast cancer will be expanded from human donors. Coupled with the T-cell profiling method developed here, these T cells provide valuable opportunities to systematically screen for optimal expansion conditions of subdominant T cells and define their molecular metrics that correlate with the best anti-tumor activity. The definition of such metrics will further simplify the quality control protocol and facilitate the standardization of the ACT manufacturing process. |
| 资源类型: | 项目
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/91190
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| Appears in Collections: | 全球变化的国际研究计划
科学计划与规划
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| Recommended Citation: | |
Fei Wen. EAGER: Biomanufacturing: Towards Reproducible and Scalable Biomanufacturing of Tumor-Specific T Cells with Optimal Phenotype and Function for Personalized Immunotherapy. 2016-01-01.
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