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

doi:10.1016/j.isci.2023.106143

HMGB1/GPC3 dual targeting vaccine induces dendritic cells-mediated CD8⁺T cell immune response and elicits potential therapeutic effect in hepatocellular carcinoma

iScience. 2023 Feb 4;26(3):106143. doi: 10.1016/j.isci.2023.106143. eCollection 2023 Mar 17.

Authors

Xiaoqing Shi¹, Jiage Ding^{2

3

4}, Yanyan Zheng^{3

4

5}, Jiawei Wang^{3

4}, Navid Sobhani⁶, Praveen Neeli⁶, Gang Wang^{3

4

5}, Junnian Zheng^{4

5}, Dafei Chai^{3

5

6}

Affiliations

¹ Department of General Surgery, Lianyungang Hospital of Traditional Chinese Medicine, Lianyungang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Lianyungang, Jiangsu 222004, China.
² Department of Oncology, Xuzhou Central Hospital, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221009, China.
³ Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China.
⁴ Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, China.
⁵ Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China.
⁶ Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.

Abstract

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.

Keywords: cancer; immunology.