Manganese-mineralized cancer cells as immunogenic cancer vaccines for tumor immunotherapy

Abstract

The strategy of using tumor cells to construct whole-cell cancer vaccines has received widespread attention. However, the limited immunogenicity of inactivated tumor cells and the challenge of overcoming immune suppression in solid tumors have hindered the application of whole-cell-based cancer immune therapy. Inspired by the regulatory effects of MnO₂ and spatiotemporal control capability of material layers in cell surface engineering, we developed a manganese (Mn)-mineralized tumor cell, B16F10@MnO₂, by inactivating B16F10 melanoma cells with KMnO₄ to generate manganese-mineralized tumor cells. The cell-based composite was formed by combining amorphous MnO₂ with the membrane structure of cells based on the redox reaction between KMnO₄ and tumor cells. The MnO₂ layer induced a stronger phagocytosis of ovalbumin (OVA)-expressing tumor cells by antigen presenting cells than formaldehyde-fixed cells did, resulting in specific antigen-presentation in vitro and in vivo and subsequent immune responses. Intratumoral therapy with B16F10@MnO₂ inhibited B16F10 tumor growth. Moreover, the infiltration of CD8⁺ T cells within B16F10 solid tumors and the proportion of central memory T cells both increased in B16F10@MnO₂ treated tumor-bearing mice, indicating enhanced adaptive immunity. This study provides a convenient and effective method to improve whole-cell-based anti-tumor therapy.