Dendritic cell-based vaccine prepared with recombinant Lactococcus lactis eukaryotic-prokaryotic dual expressing OVA enhances antitumor efficacy by both direct and cross-presentation

文献类型： 外文期刊

第一作者： Zhang, Tingting

作者： Zhang, Tingting;Huang, Shuai;Liu, Peng;Su, Xiaoqiu;Zou, Jiahe;Wu, Yulin;Li, Yijie;Xu, Yuekang;Li, Jinyao;Zhang, Tingting

作者机构：

关键词： Dendritic cell-based vaccine; Lactococcus lactis; Eukaryotic-prokaryotic dual expression; Antigen cross-presentation; Antitumor efficacy

期刊名称：INTERNATIONAL IMMUNOPHARMACOLOGY （ 影响因子：4.7； 五年影响因子：5.0 ）

ISSN： 1567-5769

年卷期： 2025 年 163 卷

页码：

收录情况： SCI

摘要： Probiotic Lactococcus lactis (L.L) can act as an antigen delivery carrier to cross-present (XPT) exogenous antigens in dendritic cells (DCs). To optimize antigen XPT in a DC-based vaccine for improved antitumor efficacy, we produced recombinant L.L strains expressing the model antigen OVA via distinct methods: prokaryotic expression alone, eukaryotic expression alone, or dual prokaryotic-eukaryotic expression (designated pOVA-L.L, eOVA-L.L, and dOVA-L.L, respectively). These strains were used to deliver antigens into DCs. Although all three recombinant OVA-L.L strains significantly enhanced DCs' ability to promote OT-I cell proliferation (with dOVA-L.L-treated DCs (dOVA-L.L-DCs) showing the strongest effect), only dOVA-L.L-DCs demonstrated significantly more potent antitumor efficacy in the B16-OVA tumor mouse model, consistent with the in vitro data. Further investigation into the mechanisms underlying the enhanced antigen XPT and anti-tumor efficacy of dOVA-L.L-DCs revealed that pOVA-L.L and dOVA-L.L resided both inside and outside lysosomes, whereas eOVA-L.L was located exclusively outside lysosomes. Consequently, dOVA-L.L-DCs could XPT higher amounts of MHC I-OVA peptide complex on their surface. Furthermore, these DCs could also directly present lysosome-derived OVA peptide-MHC II complexes to stimulate antigen-specific CD4+ T cell responses in vivo. Collectively, these mechanisms induced more persistent cellular immune responses than either of the other two recombinant L.L-DCs. In conclusion, we developed an enhanced antigen delivery system using probiotic food-grade bacteria. This system promotes the prolonged expression of exogenous antigens and significantly enhances the XPT capacity of DC vaccines for tumor immunotherapy.

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