The development of multi-functional enzyme-based therapy against Triple Negative Breast Cancer

针对三阴性乳腺癌的多功能酶疗法的开发

• 批准号: 22KJ1057
• 负责人: 黄 薇恩
• 金额: $ 1.6万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2023
• 资助国家: 日本
• 起止时间: 2023-03-08 至 2025-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22KJ1057/
• 关键词: Breast cancer; TAM; Macrophage polarization; RaPID

Firstly, I wanted to identify the macrocyclic peptides against Colony-Stimulating Factor-1 Receptor expressed on the macrophage. The activation from macrophage colony stimulating factor emitted form cancer cell would induce the polarization of immunostimulatory macrophage to immunosuppressive Tumor-Associated Macrophage. The RaPID mRNA display was applied to discover the peptides binder to biotinylated MCSF immobilized on streptavidin magnetic beads. The selection was conducted for five consecutive rounds including the positive rounds with MCSF immobilized beads and negative rounds with empty biotin masked streptavidin magnetic beads. Based on the next generation sequencing results, the majority of acquired binders results did not show difference between positive and negative rounds.

首先，我想鉴定巨噬细胞上表达的抗集落刺激因子-1受体的大环肽。肿瘤细胞释放的巨噬细胞集落刺激因子的激活可诱导免疫刺激型巨噬细胞向免疫抑制型肿瘤相关巨噬细胞极化。应用RaPID mRNA显示技术发现了固定在链霉亲和素磁珠上的生物素化MCSF的肽结合物。连续5轮筛选，阳性组采用MCSF固定磁珠，阴性组采用空生物素掩盖链霉亲和素磁珠。根据下一代测序结果，大多数获得的结合物结果在阳性和阴性轮次之间没有差异。