Human β-defensin-2 Enhances Anti-tumor Efficacy of Survivin-based Broad-spectrum DNA Vaccine in Mouse Tumor Model
LUO Yan-xi1
WANG Ming-long2
WANG Shi-bing3
SUN Ting1
XIE Tian4
YAN Hui1
1.Institute of Materia Medica,Hangzhou Medical College,Hangzhou 310013,China2.Department of Surgical Oncology,the First Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310003,China3.Molecular Diagnosis Laboratory,Zhejiang Provincial People's Hospital,People's Hospital of Hangzhou Medical College,Hangzhou 310013,China4.Holistic Integrative Pharmacy Institutes,Hangzhou Normal University,Hangzhou 310013,China
摘要：Objective: Malignant tumors greatly endanger and affect the quality of human life. Among antitumor biotherapy strategies, DNA vaccines hold promise in part because of their unique advantages. In this study, an effective broad-spectrum antitumor DNA vaccine expressing human survivin T34A dominant-negative mutant fused with humanβ-defensin-2 (HBD2) was investigated. Methods: The expression profiles of genes of interest were examined using western blotting, reverse transcription-polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay (ELISA) in vitro. The immune function of the fusion gene vaccine (FGV) was assessed in BALB/c mice, which included detection of serum antibody, spleen lymphocyte proliferation, interferon-gamma (IFN-γ) secretion, and lactate dehydrogenase (LDH) release. In vivo antitumor effects of FGV were examined in a mouse breast cancer (4T1) model, whereas in vitro effects were assessed using tumor cells derived from different origins. Caspase-3 activity in tumor cells was also assessed after vaccine transfection. Results: The FGV triggered humoral as well as cellular immune responses against survivin. It exhibited more potent inhibition of tumor growth as well as prolonged the survival of immunized mice compared to mice immunized with only either survivin T34A or HBD2 vaccines. In addition, FGV displayed stronger cytotoxicity against tumor cells derived from different origins compared to the other vaccines and facilitated increased caspase-3 activity in transfected tumor cells. Conclusion: The novel DNA vaccine consisting of a fusion of the universal tumor antigen survivin T34A mutant with molecular adjuvant HBD2 generates enhanced broad-spectrum antitumor efficacy against cancers derived from various origins.
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分类号：R392.1(医学免疫学)
论文发表日期：2021-12-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：14( 139-151,171 )
英文信息