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开发产生抗GD2抗体的介酶干细胞作为细胞免疫疗法

Masafumi Iguchi^1,2, Shigeki Yagyu³, Kosuke Kambe^4,2

¹Department of Pediatric Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan; micloud@koto.kpu-m.ac.jp.

Anticancer research

|May 29, 2023

概括

研究人员开发了新的介质干细胞 (MSCs),可以分泌针对disialoganglioside GD2 (anti-GD2-MSCs) 的抗体. 这些工程MSCs在体外表现出对神经母细胞瘤细胞的增强自然杀手细胞活性,显示出免疫治疗的潜力.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
干细胞生物学干细胞生物学

背景情况:

之前的工作在神经母细胞瘤 (NB) 模型中确定了介质干细胞 (MSC) 和它们的抗瘤作用.
表达IFN-β的小鼠MSCs (mMSCs) 在体内显示出抗瘤特性.

研究的目的:

开发用于分泌抗-disialoganglioside GD2 (抗-GD2) 抗体的新型MSC.
评估这些抗GD2-MSCs的体外抗瘤疗效.

主要方法:

产生了一种抗GD2抗体构造 (14.G2a-Fcx2-GFP) 用于向mMSC转化.
通过GFP表达和抗体分泌通过Westernblotting评估了转导效率.
使用流细胞计证实了抗体结合能力,并评估了与人类NB细胞和NK细胞的抗体依赖性细胞毒性 (ADCC).

主要成果:

抗GD2-MSCs的转导效率超过了90%.
工程MSCs分泌功能性抗GD2抗体,对表达GD2的NB细胞具有很高的亲和力.
ADCC分析显示,在添加分泌的抗体后,NK细胞对NB细胞的细胞毒性显著增强.

结论:

新开发的抗GD2-MSCs在NB细胞上产生向GD2的功能性抗体.
这些抗体有效诱导ADCC介导的细胞毒性.
基于抗GD2-MSC的免疫疗法为具有挑战性的神经母细胞瘤病例提供了有前途的治疗策略.

关键词:

反-GD2 抗体的抗体药物输送是药物输送的过程.免疫疗法免疫疗法中介细胞干细胞中介细胞干细胞.神经母细胞瘤的神经母细胞瘤

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