Title: Bioengineered Nanocage from HBc Protein for Combination Cancer Immunotherapy

Authors: Wenjun Shan†, Haiping Zheng‡, Guofeng Fu‡, Chenfeng Liu‡, Zizhen Li§, Yuhan Ye∥, Jie Zhao†, Dan Xu†, Liping Sun†, Xin Wang§, Xiao Lei Chen‡, Shengli Bi⊥, Lei Ren*† , and Guo Fu*

Abstract:

Protein nanocages are promising multifunctional platforms for nanomedicine owing to the ability to decorate their surfaces with multiple functionalities through genetic and/or chemical modification to achieve desired properties for therapeutic and diagnostic purposes. Here, we describe a model antigen (OVA peptide) that was conjugated to the surface of a naturally occurring hepatitis B core protein nanocage (HBc NC) by genetic modification. The engineered OVA-HBc nanocages (OVA-HBc NCs), displaying high density repetitive array of epitopes in a limited space by self-assembling into symmetrical structure, not only can induce bone marrow derived dendritic cells (BMDC) maturation effectively but also can be enriched in the draining lymph nodes. Naïve C57BL/6 mice immunized with OVA-HBc NCs are able to generate significant and specific cytotoxic T lymphocyte (CTL) responses. Moreover, OVA-HBc NCs as a robust nanovaccine can trigger preventive antitumor immunity and significantly delay tumor growth. When combined with a low-dose chemotherapy drug (paclitaxel), OVA-HBc NCs could specifically inhibit progression of an established tumor. Our findings support HBc-based nanocages with modularity and scalability as an attractive nanoplatform for combination cancer immunotherapy.

Full-link:https://pubs.acs.org.ccindex.cn/doi/10.1021/acs.nanolett.8b04722