Radioactive Hydroxyapatite Microspheres Empower Sustainable <i>In Situ</i> Tumor Vaccination
Pei Xu, Yuan Gu, Chenze Li, Jiahao Shen, Xiaju Cheng, Leshuai W. Zhang, Yangyun Wang, Yangyun Wang, Yong Wang, Yong Wang
Abstract
Tumor in situ vaccination (ISV) strategies have emerged in clinical trials as promising approaches, involving the release of tumor antigens through local radiotherapy and intratumorally adjuvant injections. However, the current fabrication strategy for achieving a sustainable immune response to ISV remains a pressing challenge. In this study, we present an empowered sustainable ISV method for antitumor therapy using 177 Lu-labeled manganese-doped mesoporous hydroxyapatite ( 177 Lu/Mn-HAP) microspheres. The ISV enables the sustained utilization of tumor antigens, leading to the activation of dendritic cells and polarization of macrophages toward the M1 subtype. Consequently, it facilitates the generation of potent CD8 + T-cell responses, enhancing the antitumor effects of internal radiation in both primary and distant tumors. Importantly, this approach achieves complete remission in all tumor-bearing mice and stimulates immune memory to prevent tumor recurrence. Our study highlights a universal and safe ISV strategy capable of inducing potent tumor-specific and sustainable immune response.