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一种基于纳米载体的体外 B 细胞抗原装载系统;通过体内输注载有抗原的 B 细胞抑制肿瘤生长

英文原题:An in vitro nanocarrier-based B cell antigen loading system; tumor growth suppression via transfusion of the antigen-loaded B cells in vivo.

查看英文原题

An in vitro nanocarrier-based B cell antigen loading system; tumor growth suppression via transfusion of the antigen-loaded B cells in vivo.

PubMed 2025/01/07(内容时间) Int J Pharm Q1 · IF 6(JCR 2025)

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中文摘要

基于B细胞的疫苗有望成为基于DC的疫苗的替代方案。然而,B细胞在体外对抗原的摄取效率相对较低,在基于B细胞的疫苗能够在临床环境中可行之前,必须建立高效的抗原负载方法。

我们最近开发了一种体外系统,可通过用羟基PEG修饰的脂质体(HO-PEG-Lips)将抗原高效负载到分离的脾B细胞中。因此,本研究的目的是扩展该系统,以实现另一种体内抑制肿瘤生长的方法。通过使用HO-PEG-Lips作为模型抗原OVA及佐剂α-半乳糖神经酰胺(GC)的载体,与游离OVA和游离GC相比,体外B细胞的抗原负载量增加。输注经包裹OVA和GC的HO-PEG-Lips处理的B细胞,通过强烈诱导OVA特异性T细胞,在体内抑制了表达OVA的小鼠胸腺瘤(E.G7-OVA)肿瘤的生长。在荧光显微镜观察下,证实了输注的B细胞在受体小鼠脾脏中的迁移。

我们的结果表明,我们的新型抗原负载系统可能成为一种有前景的方法,促进利用B细胞作为替代APC的细胞治疗性癌症疫苗的开发。

展开英文摘要原文

B cell-based vaccines are expected to provide an alternative to DC-based vaccines.

However, the efficacy of antigen uptake by B cells in vitro is relatively low, and efficient antigen-loading methods must be established before B cell-based vaccines are viable in clinical settings.

We recently developed an in vitro system that efficiently loads antigens into isolated splenic B cells via liposomes decorated with hydroxyl PEG (HO-PEG-Lips).

Therefore, the purpose of this study was to expand this system in order to achieve another approach to in vivo tumor growth suppression. By using HO-PEG-Lips as a carrier for model antigen OVA along with an adjuvant, α-galactosylceramide (GC), the amount of antigen loading to the B cells in vitro was increased compared with that of both free OVA and free GC.

Transfusion of B cells treated with HO-PEG-Lips that encapsulated OVA and GC suppressed the growth of OVA-expressing murine thymoma (E. G7-OVA) tumors in vivo through strong induction of OVA-specific T cells. Under fluorescence microscopic observation, migration of the transfused B cells in the spleens of recipient mice were confirmed.

Our results indicate that our novel antigen-loading system could become a promising approach to facilitate the development of cell-based therapeutic cancer vaccines utilizing B cells as alternative APCs.

论文信息

作者
Kawaguchi Y、Shimizu T、Takata H、Ando H、Ishida T
第一作者单位
Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan.Japan
通讯作者单位
Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan; Innovative Research Center for Drug Delivery System, Institute of Biomedical Sciences, Tokushima University, 770-8505 Tokushima, Japan. Electronic address: ishida@tokushima-u.ac.jp.Japan
期刊
International journal of pharmaceutics2025 Feb 10
原文标识
PubMed 39788395 · DOI 10.1016/j.ijpharm.2025.125189