Development of a Cascade-Targeting Oral Vaccine via Glycoprotein 2 on Intestinal Microfold Cells for Cancer Immunotherapy

作者：Wanqiong Li, Xin Yang, Mengfan Wang, Zheng Hu, Shaomeng Chen, Xinghua Sui, Danhong Chen, Xiaoshuang Niu, Juan Liu, Youmei Xiao, Xiuman Zhou, Guanyu Chen, Yanfeng Gao · 发表于：Nano Letters · 年份：2025 · DOI：10.1021/acs.nanolett.4c06123 · 被引用次数：9 · 研究领域：Immunotherapy and Immune Responses、Transgenic Plants and Applications、Immune Cell Function and Interaction

Oral cancer vaccines are convenient and safe, with the presence of gut-associated lymphoid tissue (GALT) involved intestinal Peyer’s patch (PPs) containing microfold (M) cells and housing abundant underneath dendritic cells (DCs). Here, we found that the endocytic receptors glycoprotein 2 (GP2) and dectin-1 are respectively expressed on M cells and DCs with high specificity. Then, we discovered a gastrointestinal hydrolysis-resistant D-peptide D GPBP-2(1-8) targeting GP2 by phage display screening and optimization. D GPBP-2(1-8) was conjugated to β-glucan (dectin-1 ligand)-containing yeast capsules (GP2-YCs) to design a cascade-targeting oral vaccine platform, which can help the antigen to efficiently cross intestinal M cells and subsequently be endocytosed by underneath DCs, thus activating CD8 + T cells. More importantly, this oral vaccine can evoke not only cellular but also humoral and mucosal immune responses. Therefore, this cascade-targeting oral vaccine could serve as a novel platform for cancer immunotherapy and infectious disease prevention as well.