Engineering PEG10-assembled endogenous virus-like particles with genetically encoded neoantigen peptides for cancer vaccination
Ruijing Tang,
Luobin Guo,
Tingyu Wei,
Tingting Chen,
Huan Yang,
Honghao Ye,
Fangzhou Lin,
Yongyi Zeng,
Haijun Yu,
Zhixiong Cai,
Xiaolong Liu
Affiliations
Ruijing Tang
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China; The Liver Center of Fujian Province, Fujian Medical University, Shanghai, China; Mengchao Med-X Center, Fuzhou University, Fuzhou, China
Luobin Guo
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China; The Liver Center of Fujian Province, Fujian Medical University, Shanghai, China; Mengchao Med-X Center, Fuzhou University, Fuzhou, China
Tingyu Wei
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China; The Liver Center of Fujian Province, Fujian Medical University, Shanghai, China; Mengchao Med-X Center, Fuzhou University, Fuzhou, China
Tingting Chen
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China; The Liver Center of Fujian Province, Fujian Medical University, Shanghai, China; Mengchao Med-X Center, Fuzhou University, Fuzhou, China
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China; The Liver Center of Fujian Province, Fujian Medical University, Shanghai, China; Mengchao Med-X Center, Fuzhou University, Fuzhou, China
Honghao Ye
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China; The Liver Center of Fujian Province, Fujian Medical University, Shanghai, China; Mengchao Med-X Center, Fuzhou University, Fuzhou, China
Fangzhou Lin
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China; The Liver Center of Fujian Province, Fujian Medical University, Shanghai, China; Mengchao Med-X Center, Fuzhou University, Fuzhou, China
Yongyi Zeng
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China; The Liver Center of Fujian Province, Fujian Medical University, Shanghai, China; Mengchao Med-X Center, Fuzhou University, Fuzhou, China
Haijun Yu
State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China; The Liver Center of Fujian Province, Fujian Medical University, Shanghai, China; Mengchao Med-X Center, Fuzhou University, Fuzhou, China
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China; The Liver Center of Fujian Province, Fujian Medical University, Shanghai, China; Mengchao Med-X Center, Fuzhou University, Fuzhou, China
Tumor neoantigen peptide vaccines hold potential for boosting cancer immunotherapy, yet efficiently co-delivering peptides and adjuvants to antigen-presenting cells in vivo remains challenging. Virus-like particle (VLP), which is a kind of multiprotein structure organized as virus, can deliver therapeutic substances into cells and stimulate immune response. However, the weak targeted delivery of VLP in vivo and its susceptibility to neutralization by antibodies hinder their clinical applications. Here, we first designed a novel protein carrier using the mammalian-derived capsid protein PEG10, which can self-assemble into endogenous VLP (eVLP) with high protein loading and transfection efficiency. Then, an engineered tumor vaccine, named ePAC, was developed by packaging genetically encoded neoantigen into eVLP with further modification of CpG-ODN on its surface to serve as an adjuvant and targeting unit to dendritic cells (DCs). Significantly, ePAC can efficiently target and transport neoantigens to DCs, and promote DCs maturation to induce neoantigen-specific T cells. Moreover, in mouse orthotopic liver cancer and humanized mouse tumor models, ePAC combined with anti-TIM-3 exhibited remarkable antitumor efficacy. Overall, these results support that ePAC could be safely utilized as cancer vaccines for antitumor therapy, showing significant potential for clinical translation.
