Engineering bioactive mineralized tumor cells for tumor immunotherapy

用于肿瘤免疫治疗的生物活性矿化肿瘤细胞工程

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Abstract

INTRODUCTION: Whole-cell tumor vaccines are advantageous because of their ability to induce a broad and multifaceted immune response through the presentation of a wide range of tumor antigens, thereby enhancing the ability of the immune system to recognize and target cancerous cells. METHOD: In this study, we present a multifunctional vaccine that consists of manganese-mineralized tumor cells and positively charged polymer-immobilized CpG. The Mn(2+) and CpG released from the engineered vaccine facilitate the maturation of dendritic cells through the activation of the cGAS-STING and TLR9 pathways, respectively. RESULT: As a consequence, the engineered vaccine derived from B16F10 cells exhibited a pronounced tumor-suppressive effect, reducing the tumor volume to approximately one-fifth of that in the control group, and significantly extending survival to day 30 in B16F10 tumor-bearing mice. This superior therapeutic outcome is associated with enhanced activation of dendritic cells, increased infiltration of NK and CD8(+) T cells, and increased production of immune cytokines within the tumor microenvironment. DISCUSSION: Together, our study highlights the immense potential of engineering bioactive mineralized tumor cells to facilitate whole-cell tumor vaccine-based immunotherapy.

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