Dual-Antigen-Loaded Hepatitis B Virus Core Antigen Virus-like Particles Stimulate Efficient Immunotherapy Against Melanoma
Keman Cheng, Tao Du, Yao Li, Yingqiu Qi, Huan Min, Yazhou Wang, Qiang Zhang, Chufan Wang, Yaming Zhou, Lihuang Li, Shefang Ye, Xi Zhou, Shengli Bi, Jun Yang, Lei Ren
Abstract
Tumor cells are rich in antigens, which provide a reliable antigen library for the design of personalized vaccines. However, an effective tumor vaccine vector that can efficiently deliver antigens to lymphoid organs to stimulate strong CD8+ cytotoxic T-lymphocyte immune response is still lacking. Here we designed a dual-antigen delivery system based on hepatitis B virus core antigen virus-like particles (HBc VLPs). We first confirmed that different antigen-loaded HBc VLP monomers could be assembled into nanoparticles (hybrid VLPs). Hybrid VLPs could slightly enhance bone marrow-derived dendritic cell maturation in vitro. Strikingly, hybrid VLPs could generate antigen-specific antitumor immunity and innate immunity in vivo which could significantly inhibit tumor growth or metastatic formation in a subcutaneous tumor or lung metastatic tumor model, respectively. Moreover, dual-epitope vaccination generated enhanced T-cell responses that potently inhibited tumor growth and metastatic formation. Together, this study provides a new powerful concept for cancer immunotherapy and suggests a novel design for VLP-based personalized nanomedicine.