| 项目编号: | 1547638
|
| 项目名称: | EAGER: Biomanufacturing: Physiologically-inspired Large Scale Manufacturing and Potency-Biomarker identification for Chimeric Antigen Receptor (CAR)-T cells |
| 作者: | Krishnendu Roy
|
| 承担单位: | Georgia Tech Research Corporation
|
| 批准年: | 2014
|
| 开始日期: | 2015-09-01
|
| 结束日期: | 2018-08-31
|
| 资助金额: | USD300000
|
| 资助来源: | US-NSF
|
| 项目类别: | Standard Grant
|
| 国家: | US
|
| 语种: | 英语
|
| 特色学科分类: | Engineering - Chemical, Bioengineering, Environmental, and Transport Systems
|
| 英文关键词: | t cell
; cell
; car-t
; efficient paracrine/autocrine signaling
; product quality
; synthetic lymph-node-like niche
; comprehensive characterization
; cell potency
; various cell-seeding density
; large scale expansion
; critical importance
; dynamic culture
; synthetic 3d microenvironment
; close cell-cell contact
; il requirement
; eager project
; biologically-inspired strategy
; overall manufacturing cost
; expansion potential
; routine analysis tool
; perfusion bioreactor
; high density
; current t-cell manufacturing concept
; large amount
; cost effectiveness
; culture media
; anti-cd28-functionalized microcarrier
; anti-cd28 ligand density
; robust correlative marker
|
| 英文摘要: | 1547638
Roy, Krishnendu
A novel, biologically-inspired strategy is proposed to enhance the expansion of therapeutic T cells by mimicking the environment and conditions of lymph nodes, where these cells normally expand in the body. This idea of T cell expansion inside synthetic lymph-node-like niches, where cells communicate with each other and with 'self' is unique, but firmly rooted on physiological principles. Our approach could vastly enhance the expansion potential of T cells making larger numbers of them available for therapy and also reduce overall manufacturing cost, making the treatment more affordable and widely available. Further, predictively measuring the efficacy and potency of these manufactured T cells, before infusing them in patients, is of critical importance. A comprehensive characterization of manufactured T cells will be carried out to develop robust correlative markers that can predict cell potency and can eventually be used as a routine analysis tool to determine the quality of these cells before infusion.
This EAGER project will investigate human CAR-T cell expansion within synthetic 3D microenvironments that mimic the T cell niches within lymph nodes (LN). Anti-CD3/anti-CD28-functionalized microcarriers will be used and human CAR-T cells will be cultured in LN-mimicking 3D niches where T cells remain at high density with close cell-cell contact, and allow efficient paracrine/autocrine signaling. These parameters, absent from the current T-cell manufacturing concepts, are critical since T cells secrete large amounts of interleukins (ILs) locally to promote rapid, large scale expansion. Thus, this approach could also reduce culture media and IL requirements, thereby significantly reducing cost. The effect of low O2 tension will be evaluated together with various cell-seeding densities and anti-CD3/anti-CD28 ligand densities on expansion efficacy and T cell quality. Further, the LN-like niche will be combined with stirred tank or perfusion bioreactors, to determine whether dynamic culture and flow perfusion improve expansion efficacy, product quality, scalability and cost effectiveness. |
| 资源类型: | 项目
|
| 标识符: | http://119.78.100.158/handle/2HF3EXSE/93436
|
| Appears in Collections: | 影响、适应和脆弱性
气候减缓与适应
|
|
There are no files associated with this item.
|
| Recommended Citation: | |
Krishnendu Roy. EAGER: Biomanufacturing: Physiologically-inspired Large Scale Manufacturing and Potency-Biomarker identification for Chimeric Antigen Receptor (CAR)-T cells. 2014-01-01.
|
|
|