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具有改善免疫原性和迁移表型的肿瘤靶向树突状细胞疫苗的制备

英文原题:Generation of Tumor Targeted Dendritic Cell Vaccines with Improved Immunogenic and Migratory Phenotype.

查看英文原题

Generation of Tumor Targeted Dendritic Cell Vaccines with Improved Immunogenic and Migratory Phenotype.

PubMed 2022/01/01(内容时间) Methods Mol Biol

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中文摘要

我们团队已采用多种方法,为原发性恶性脑肿瘤患者有效体外生成树突状细胞(DC)疫苗。为了可靠地制备出最具效力、最具代表性的疫苗接种DC,从而引发抗肿瘤反应,需要能够统筹多种方法,以解决抗原交叉呈递、T细胞共刺激与极化以及迁移能力等问题。在本章中,我们描述了一种增强DC免疫原性和迁移潜能、以用于疫苗的新方法。我们阐明了在制备癌症疫苗时避免所谓免疫优势现象的方法。我们发现,在整个分化方案期间将DC祖细胞在无血清条件下培养,可获得更均一成熟的DC群体,与在含血清培养条件下生成的DC相比,其表现出增强的免疫原性。此外,我们展示了使用CCL3蛋白生成高迁移性DC的方法,这些DC易于向淋巴器官趋化因子迁移。这两种方法的结合代表了一种简便且临床上可行的策略,用于生成具有优异迁移能力的高度成熟DC。

展开英文摘要原文

Our group has employed methodologies for effective ex vivo generation of dendritic cell (DC) vaccines for patients with primary malignant brain tumors.

In order to reliably produce the most potent, most representational vaccinated DC that will engender an antitumor response requires the ability to orchestrate multiple methodologies that address antigen cross-presentation, T-cell costimulation and polarization, and migratory capacity. In this chapter, we describe a novel method for augmenting the immunogenicity and migratory potential of DCs for their use as vaccines.

We have elucidated methodologies to avoid the phenomenon known as immunodominance in generating cancer vaccines.

We have found that culturing DC progenitors in serum-free conditions for the duration of the differentiation protocol results in a more homogeneously mature population of DCs that exhibit enhanced immunogenicity compared to DCs generated in serum-containing culture conditions.

Furthermore, we demonstrate our method for generating high mobility DCs that readily migrate toward lymphoid organ chemoattractants using CCL3 protein. The combination of these two approaches represents a facile and clinically tractable methodology for generating highly mature DCs with excellent migratory capacity.

论文信息

作者
Swartz AM、Hotchkiss KM、Nair SK、Sampson JH、Batich KA
第一作者单位
Division of Surgical Sciences, Department of Surgery, Duke University Medical Center, Durham, NC, USA.United States
通讯作者单位
Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA. kristen.batich@duke.edu.United States
期刊
Methods in molecular biology (Clifton, N.J.)2022
原文标识
PubMed 34914072 · DOI 10.1007/978-1-0716-1884-4_33