Implantable Synthetic Immune Niche for Spatiotemporal Modulation of Tumor-derived Immunosuppression and Systemic Antitumor Immunity: Postoperative Immunotherapy
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Rationally designed biomaterial-based immune niches that can spatiotemporal modulate immunosuppressive factors in tumor microenvironment is increasingly recognized to have key roles for improving current cancer immunotherapy. Here, an implantable 3-dimensional porous scaffold was designed to generate synergistic action between myeloid-derived suppressor cell-depleting agents, which can revert an immunosuppressive microenvironment to one supporting anti-tumor immunity, and cancer vaccines consisting of whole tumor lysates and nanogel-based adjuvants, which can generate tumor antigen-specific T cell responses. The local peritumoral implantation of the synthetic immune niche (termed immuneCare-DISC, iCD) as a post-surgical treatment in an advanced-stage primary 4T1 breast tumor model generated systemic anti-tumor immunity and inhibited tumor relapse and metastasis, resulting in 100% survival.