4.8 Article

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

Journal

ADVANCED SCIENCE
Volume -, Issue -, Pages -

Publisher

WILEY
DOI: 10.1002/advs.202305081

Keywords

antitumor immunity; beta-glucan; cancer vaccines; probiotics; trained immunity

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This study developed a personalized cancer vaccine by engineering inactivated probiotic Escherichia coli Nissle 1917 to load tumor antigens and beta-glucan, a trained immunity inducer. The vaccine efficiently integrates trained immunity and adaptive immunity, generating strong prophylactic and therapeutic effects to inhibit tumor growth. It also prevents postoperative tumor recurrence by delivering autologous tumor antigens.
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 beta-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.

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