A comprehensive platform for ex vivo T-cell expansion based on biodegradable polymeric artificial antigen-presenting cells
A comprehensive platform for ex vivo T-cell expansion based on biodegradable polymeric artificial antigen-presenting cells
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DOI：
10.1038/mt.2008.11
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发表时间：
2008-04-01
影响因子：
12.4
通讯作者：
Fahmy, Tarek M.
中科院分区：
文献类型：
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作者：
Steenblock, Erin R.;Fahmy, Tarek M.
有效的t细胞刺激和增殖对特定抗原的反应是对抗传染病和癌症的免疫治疗的目标。操纵这种反应可以通过过继免疫疗法来完成，包括输注抗原特异性t细胞群和抗原提呈细胞在体外扩增。我们在由聚乳酸-羟基乙酸酯（PLGA）构成的可生物降解微粒上模拟生理抗原呈递，聚乳酸-羟基乙酸酯（PLGA）是一种安全性已被确定用于人体的聚合物体系。这些颗粒具有高密度的接头元件，可将识别配体和共刺激配体连接到包裹细胞因子白介素-2 （IL-2）的可生物降解核心上。我们证明了该系统在有效的多克隆和抗原特异性t细胞刺激和扩增中的效用，表明与外源性细胞因子的作用相比，在t细胞接触附近持续释放IL-2显着提高了这些非细胞系统的刺激能力。这导致t细胞扩增增加45倍。此外，这种抗原呈递模式使扩增偏向CD8(+) t细胞表型。这种综合的非细胞平台，能够传递识别、共刺激和细胞因子信号，代表了一种有前途的人工抗原呈递新技术。
Efficient T-cell stimulation and proliferation in response to specific antigens is a goal of immunotherapy against infectious disease and cancer. Manipulation of this response can be accomplished by adoptive immunotherapy involving the infusion of antigen-specific T-cell populations expanded ex vivo with antigen presenting cells. We mimicked physiological antigen presentation on a biodegradable microparticle constructed from poly(lactide-co-glycolide) (PLGA), a polymer system whose safety has been established for use in humans. These particles present a high density of adaptor elements for attaching both recognition ligands and co-stimulatory ligands to a biodegradable core encapsulating the cytokine interleukin-2 (IL-2). We demonstrate the utility of this system in efficient polyclonal and antigen-specific T-cell stimulation and expansion, showing that sustained release of IL-2 in the vicinity of T-cell contacts dramatically improves the stimulatory capacity of these acellular systems, as compared to the effect of exogenous addition of cytokine. This results in a 45-fold enhancement in T-cell expansion. In addition, this mode of antigen presentation skews the expansion toward the CD8(+) T-cell phenotype. This comprehensive acellular platform, capable of delivering recognition, costimulatory, and cytokine signals, represents a promising new technology for artificial antigen presentation.