Engineered Probiotic‐Based Personalized Cancer Vaccine Potentiates Antitumor Immunity through Initiating Trained Immunity

• Published in: Advanced science 2024-01, Vol.11 (3), p.e2305081-n/a
• Main Authors: Chen, Zhaoxia, Yong, Tuying, Wei, Zhaohan, Zhang, Xiaoqiong, Li, Xin, Qin, Jiaqi, Li, Jianye, Hu, Jun, Yang, Xiangliang, Gan, Lu
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Antigens; Antigens, Neoplasm; antitumor immunity; Bacteria; Cancer Vaccines; Cytokines; Dendritic Cells; Epigenetics; High temperature; Humans; Immunotherapy; Lymphocyte Activation; Lymphocytes; Neoplasms - therapy; Pathogens; Probiotics; Probiotics - therapeutic use; Trained Immunity; Tumor Microenvironment; Tumor necrosis factor-TNF; β‐glucan
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202305081

Cancer vaccines hold great potential for clinical cancer treatment by eliciting T cell‐mediated immunity. However, the limited numbers of antigen‐presenting cells (APCs) at the injection sites, the insufficient tumor antigen phagocytosis by APCs, and the presence of a strong tumor immunosuppressive microenvironment severely compromise the efficacy of cancer vaccines. Trained innate immunity may promote tumor antigen‐specific adaptive immunity. Here, a personalized cancer vaccine is developed by engineering the inactivated probiotic Escherichia coli Nissle 1917 to load tumor antigens and β‐glucan, a trained immunity inducer. After subcutaneous injection, the cancer vaccine delivering model antigen OVA (BG/OVA@EcN) is highly accumulated and phagocytosed by macrophages at the injection sites to induce trained immunity. The trained macrophages may recruit dendritic cells (DCs) to facilitate BG/OVA@EcN phagocytosis and the subsequent DC maturation and T cell activation. In addition, BG/OVA@EcN remarkably enhances the circulating trained monocytes/macrophages, promoting differentiation into M1‐like macrophages in tumor tissues. BG/OVA@EcN generates strong prophylactic and therapeutic efficacy to inhibit tumor growth by inducing potent adaptive antitumor immunity and long‐term immune memory. Importantly, the cancer vaccine delivering autologous tumor antigens efficiently prevents postoperative tumor recurrence. This platform offers a facile translatable strategy to efficiently integrate trained immunity and adaptive immunity for personalized cancer immunotherapy. A personalized cancer vaccine is developed by engineering the inactivated probiotic Escherichia coli Nissle 1917 to load tumor antigens, and β‐glucan (BG/OVA@EcN). BG/OVA@EcN efficiently induces trained immunity in macrophages to enhance adaptive immunity. Meanwhile, BG/OVA@EcN‐augmented circulating trained monocytes/macrophages promote differentiation into M1‐like macrophages in tumor tissues, generating strong prophylactic and therapeutic efficacy to inhibit tumor growth.