CaCO3 powder-mediated biomineralization of antigen nanosponges synergize with PD-1 blockade to potentiate anti-tumor immunity
Runping Su, Jingjing Gu, Juanjuan Sun, Jie Zang, Yuge Zhao, Tingting Zhang, Yingna Chen, Gaowei Chong, Weimin Yin, Xiao Zheng, Bingbing Liu, Li Huang, Shuangrong Ruan, Haiqing Dong, Yan Li, Yongyong Li, Yongyong Li, Yongyong Li
Abstract
Abstract Antigen self-assembly nanovaccines advance the minimalist design of therapeutic cancer vaccines, but the issue of inefficient cross-presentation has not yet been fully addressed. Herein, we report a unique approach by combining the concepts of “antigen multi-copy display” and “calcium carbonate (CaCO 3 ) biomineralization” to increase cross-presentation. Based on this strategy, we successfully construct sub-100 nm biomineralized antigen nanosponges (BANSs) with high CaCO 3 loading (38.13 wt%) and antigen density (61.87%). BANSs can be effectively uptaken by immature antigen-presenting cells (APCs) in the lymph node upon subcutaneous injection. Achieving efficient spatiotemporal coordination of antigen cross-presentation and immune effects, BANSs induce the production of CD4 + T helper cells and cytotoxic T lymphocytes, resulting in effective tumor growth inhibition. BANSs combined with anti-PD-1 antibodies synergistically enhance anti-tumor immunity and reverse the tumor immunosuppressive microenvironment. Overall, this CaCO 3 powder-mediated biomineralization of antigen nanosponges offer a robust and safe strategy for cancer immunotherapy.