Abstract B133: Implantable synthetic immune hydrogel for spatiotemporal modulation of tumor-derived immunosuppression and systemic antitumor immunity

Abstract

The development of biomaterial-based immune niches that can shape tumor-induced immunosuppressive factors will play an important role to improve current cancer immunotherapy. Herein, we developed an engineered 3-dimensional porous scaffold for creating synergistic action between myeloid-derived suppressor cell (MDSC)-depleting drugs, which can revert an immunosuppressive tumor microenvironment to one supporting antitumor immunity, and cancer vaccines (whole tumor lysate-based antigens and nano-adjuvants carrying Toll-like receptor 3 agonists), which can induce tumor antigen-specific T-cell responses. The local implantation of the scaffold (called immuneCare-DISC, iCD) as a post-surgical treatment in large established 4T1 breast tumors induced systemic antitumor immunity and prevented relapse and metastasis, resulting in survival of 100%. These therapeutic results were obtained from the depletion of MDSCs by control releasing of gemcitabine and the recruitment/activation of dendritic cells, increased infiltrating of T-cells and enhanced level of IFN-γ production by sustained releasing of cancer vaccine from the iCD. This synthetic immune niche iCD as a spatiotemporal modulation of tumor-induced immunosuppression and cancer vaccine-induced immune stimulation is proposed to generate favorable environment to prevent recurrence and metastasis following the surgical resection. Citation Format: Chanyoung Song, Il Woo Shin, Long Ren, Yong Taik Lim. Implantable synthetic immune hydrogel for spatiotemporal modulation of tumor-derived immunosuppression and systemic antitumor immunity [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B133.