| 项目编号: | 1644363
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| 项目名称: | EAGER: Biomanufacturing: Creating a multifunctional nanoreagent that stimulates, genetically manipulates, and selectively expands therapeutic T cells for adoptive cell therapy |
| 作者: | Matthias Stephan
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| 承担单位: | Fred Hutchinson Cancer Research Center
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| 批准年: | 2017
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| 开始日期: | 2017-01-01
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| 结束日期: | 2018-12-31
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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
; cell
; project
; hematopoietic stem cell
; cell culture
; other therapeutic cell type
; natural killer cell
; mesenchymal stem cell
; culture
; nanoparticles
; car-t
; nanoparticle
; standard-of-care
; patient
; cost
; therapeutic lymphocyte
; hypothesis
; clinical setting
; ongoing teaching
; selective outgrowth
; approach
; nanoparticle-based method
; b lymphocyte
; same surface-anchored antigen
; considerable technical expertise
; dna-carrying nanoparticle
; genetically-modified lymphocyte population
; biomaterial impact medicine
; large-scale manufacture
; same time
; conventional approach
; major obstacle
; therapeutic efficacy
; special instrument
; obvious advantage
; new development
; stephanadoptive immunotherapy
; free nanoparticle
; united states
; outreach program
; elaborate protocol
; magnetic bead expansion
; dedicated equipment
; shuttle tumor-specific chimeric antigen receptor
; viral method
; new disease treatment option
; genetically-programmed lymphocyte
; current lymphocyte manufacturing practice
; economical commercial-scale manufacturing
; cancer patient
; multistep/multi-reagent method
; difficult procedure
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| 英文摘要: | 1644363 - Stephan
Adoptive immunotherapy is a new disease treatment option based on patient-derived immune ("T") cells that are genetically modified to target cancer or infections. This approach has already established its potential in several medical arenas. But despite the obvious advantages afforded by these targeted therapies compared to chemotherapy, radiotherapy, and surgery, the complexity and costs of producing genetically-programmed lymphocytes pose major obstacles to their use as standard-of-care. This project addresses the problem by developing microscopic "nanoparticles" that can stimulate, genetically modify, and selectively expand therapeutic lymphocytes simply by adding them to the cells in culture. Nanoparticles can be repeatedly added to the cell culture until the required numbers of engineered lymphocytes are achieved. Implementing the large-scale manufacture of targeted T cells afforded by this approach could translate into treating patients with an immunotherapy that is practical, low-cost, and broadly-applicable. Furthermore, the project will help develop the scientists of tomorrow through its participation in ongoing teaching and outreach programs designed to generate enthusiasm in students learning how new developments in biomaterials impact medicine.
Current lymphocyte manufacturing practices require an assortment of elaborate protocols to isolate, genetically modify, and selectively expand the redirected cells before infusing them back into the patient. Because these difficult procedures entail dedicated equipment and considerable technical expertise, providing this kind of personalized T cell therapy to every cancer patient in the United States is not practical. This project addresses the problem by developing microscopic "nanoparticles" that can stimulate, genetically modify, and selectively expand therapeutic lymphocytes simply by adding them to the cells in culture. The project tests the hypothesis that appropriately engineered DNA-carrying nanoparticles can efficiently shuttle tumor-specific chimeric antigen receptor (CAR) genes into cultured T cells (CAR-T cells), and at the same time induce the selective outgrowth of the genetically-modified lymphocyte population by presenting the cells with the same surface-anchored antigens that are targeted by the encoded CAR. The hypothesis is tested via two specific aims: 1) designing the proposed DNA nanocarriers and 2) comparing the functionality and therapeutic efficacy of CAR-T cells manufactured using the proposed DNA nanocarriers versus those created by the conventional approach using viral methods and magnetic bead expansion. The nanoparticle-based methods will be able to activate, engineer, and propagate T cells without special instruments, equipment, or training and could be manufactured using automated protocols that are compatible with any clinical setting, and at a fraction of the costs involved in multistep/multi-reagent methods. Nanoparticles can be repeatedly added to the culture until the required percentage of programmed T cells is achieved. They are biodegradable and biocompatible and the expanded T cells can easily be separated from free nanoparticles by centrifugation. The platform could easily be adapted to enable economical commercial-scale manufacturing of other therapeutic cell types, such as natural killer cells, hematopoietic stem cells, mesenchymal stem cells, or B lymphocytes, which substantially broadens the applicability of the approach for the treatment of disease. |
| 资源类型: | 项目
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/90681
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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: | |
Matthias Stephan. EAGER: Biomanufacturing: Creating a multifunctional nanoreagent that stimulates, genetically manipulates, and selectively expands therapeutic T cells for adoptive cell therapy. 2017-01-01.
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