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HMGB1/GPC3双靶点疫苗诱导树突状细胞介导的CD8T细胞免疫反应并在肝细胞癌中引发潜在治疗效果。

HMGB1/GPC3 dual targeting vaccine induces dendritic cells-mediated CD8T cell immune response and elicits potential therapeutic effect in hepatocellular carcinoma.

作者信息

Shi Xiaoqing, Ding Jiage, Zheng Yanyan, Wang Jiawei, Sobhani Navid, Neeli Praveen, Wang Gang, Zheng Junnian, Chai Dafei

机构信息

Department of General Surgery, Lianyungang Hospital of Traditional Chinese Medicine, Lianyungang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Lianyungang, Jiangsu 222004, China.

Department of Oncology, Xuzhou Central Hospital, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221009, China.

出版信息

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

DOI:10.1016/j.isci.2023.106143
PMID:36879804
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9984564/
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 CD8T cells and DCs. Furthermore, the PLGA/PEI-HMGB1/GPC3 vaccine induced a strong CTL effect and promoted functional CD8T cell proliferation. Intriguingly, the depletion assay proved that the therapeutic effect PLGA/PEI-HMGB1/GPC3 vaccine was dependent on antigen-specific CD8T 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 CD8T 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.

摘要

肝细胞癌（HCC）是一种致命的恶性肿瘤，但有效的临床干预措施有限。开发了编码高迁移率族蛋白B1（HMGB1）或GPC3双靶点的PLGA/PEI介导的DNA疫苗用于HCC治疗。与PLGA/PEI-GPC3免疫相比，PLGA/PEI-HMGB1/GPC3联合免疫显著抑制皮下肿瘤生长，同时增加CD8T细胞和DC的浸润。此外，PLGA/PEI-HMGB1/GPC3疫苗诱导了强烈的CTL效应并促进功能性CD8T细胞增殖。有趣的是，耗竭试验证明PLGA/PEI-HMGB1/GPC3疫苗的治疗效果依赖于抗原特异性CD8T细胞免疫反应。在再次攻击实验中，PLGA/PEI-HMGB1/GPC3疫苗通过诱导记忆性CD8T细胞反应，对侧肿瘤的生长提供了持久的抗性。总体而言，PLGA/PEI-HMGB1/GPC3疫苗可诱导强烈且持久的CTL效应，并抑制肿瘤进展或再次攻击。因此，PLGA/PEI-HMGB1/GPC3联合免疫可能是一种有效的抗HCC肿瘤策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c6/9984564/64cb32a29144/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c6/9984564/783c67714de5/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c6/9984564/1ce9aafcba00/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c6/9984564/a0f7d3816c45/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c6/9984564/e5f0b798a8a1/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c6/9984564/48eff6ccf538/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c6/9984564/64cb32a29144/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c6/9984564/783c67714de5/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c6/9984564/1ce9aafcba00/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c6/9984564/a0f7d3816c45/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c6/9984564/e5f0b798a8a1/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c6/9984564/48eff6ccf538/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c6/9984564/64cb32a29144/gr5.jpg

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