Immunogenic Material Vaccine for Cancer Immunotherapy by Structure‐dependent Immune Cell Trafficking and Modulation

Abstract

Inherently immunogenic materials offer enormous prospects in enhancing vaccine efficacy. However, the understanding and improving material adjuvanticity remain elusive. Herein we report how the structural presentation of immunopotentiators in a material governs the dynamic dialogue between innate and adaptive immunity for enhanced cancer vaccination. We precisely manipulate the immunopotentiator manganese into six differing structures that resemble the architectures of two types of pathogens (spherical viruses or rod‐like bacteria). The results reveal that innate immune cells accurately sense and respond to the architectures, of which two outperformed material candidates (151 nm hollow spheres and hollow micro‐rods with an aspect ratio of 4.5) show higher competence in creating local pro‐inflammatory environment with promoted innate immune cell influx and stimulatory effects on multiple subsets of dendritic cells (DCs). In combination with viral peptides, model proteins or cell lysate antigens, mature CD103⁺ (CD8⁺) DCs and CD11b⁺ DCs induced by the outperformed micro‐rod material remarkably primes antigen‐specific CD8⁺ and CD4⁺ cytolytic T cells, respectively. The micro‐rod stimulates DCs with enriched gene signatures associated with plasmacytoid DC, potentially contributing to enhanced type‐I interferon (IFN) mediated cellular immunity. In prophylactic and therapeutic regimens, the micro‐rod adjuvanted vaccines display optimal aptitude in tumor suppression universally in four aggressive malignant murine tumor models, by promoting the infiltration of heterogeneous cytolytic effector cells while decreasing suppressive immunoregulatory populations in tumors. This study demonstrates that a rationally selected architecture of immunogenic materials potentially advances the clinical reality of cancer vaccination .

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