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，我想鉴定针对巨噬细胞上表达的集落刺激因子 1 受体的大环肽。癌细胞释放的巨噬细胞集落刺激因子的激活会诱导免疫刺激性巨噬细胞极化为免疫抑制性肿瘤相关巨噬细胞。应用 RaPID mRNA 展示来发现与固定在链霉亲和素磁珠上的生物素化 MCSF 结合的肽。选择连续进行五轮，包括使用 MCSF 固定珠的阳性轮和使用空生物素掩蔽的链霉亲和素磁珠的阴性轮。根据下一代测序结果，大多数获得的结合物结果并未显示出阳性轮次和阴性轮次之间的差异。