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

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 ^DGPBP-2(1-8) targeting GP2 by phage display screening and optimization. ^DGPBP-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.