HMGB1/GPC3 dual targeting vaccine induces dendritic cells-mediated CD8+T cell immune response and elicits potential therapeutic effect in hepatocellular carcinoma
Xiaoqing Shi,
Jiage Ding,
Yanyan Zheng,
Jiawei Wang,
Navid Sobhani,
Praveen Neeli,
Gang Wang,
Junnian Zheng,
Dafei Chai
Affiliations
Xiaoqing Shi
Department of General Surgery, Lianyungang Hospital of Traditional Chinese Medicine, Lianyungang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Lianyungang, Jiangsu 222004, China
Jiage Ding
Department of Oncology, Xuzhou Central Hospital, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221009, China; Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, China
Yanyan Zheng
Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China
Jiawei Wang
Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, China
Navid Sobhani
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
Praveen Neeli
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
Gang Wang
Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; Corresponding author
Junnian Zheng
Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; Corresponding author
Dafei Chai
Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Corresponding author
Summary: Hepatocellular carcinoma (HCC) is a fatal malignant tumor, but effective clinical interventions are limited. PLGA/PEI-mediated DNA vaccine encoding the dual targets of high-mobility group box 1 (HMGB1) or GPC3 was developed for HCC treatment. Compared with PLGA/PEI-GPC3 immunization, PLGA/PEI-HMGB1/GPC3 co-immunization significantly inhibited the subcutaneous tumor growth, while increasing the infiltration of CD8+T cells and DCs. Furthermore, the PLGA/PEI-HMGB1/GPC3 vaccine induced a strong CTL effect and promoted functional CD8+T cell proliferation. Intriguingly, the depletion assay proved that the therapeutic effect PLGA/PEI-HMGB1/GPC3 vaccine was dependent on antigen-specific CD8+T cell immune responses. In the rechallenge experiment, PLGA/PEI-HMGB1/GPC3 vaccine provided a long-lasting resistance to the growth of the contralateral tumor by inducing the memory CD8+T cell responses. Collectively, PLGA/PEI-HMGB1/GPC3 vaccine could induce a strong and long-lasting CTL effect and inhibit the tumor progression or re-attack. Therefore, the combined co-immunization of PLGA/PEI-HMGB1/GPC3 might be served as an effective anti-tumor strategy against HCC.
