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以自噬诱导剂Beclin-1为佐剂的HPV DNA疫苗在小鼠模型中的抗肿瘤作用

Antitumor Effects of HPV DNA Vaccine Adjuvanted with Beclin-1 as an Autophagy Inducer in a Mice Model.

作者信息

Naziri Hamed, Tahamtan Alireza, Dadmanesh Maryam, Barati Mohammad, Ghorban Khodayar

机构信息

Department of Immunology, School of Medicine, Aja University of Medical Sciences, Tehran, Iran.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Iran Biomed J. 2019 Nov;23(6):388-94. doi: 10.29252/ibj.23.6.388. Epub 2019 May 20.

Abstract

BACKGROUND

There is a growing interest in development of an effective adjuvant system for improving DNA vaccines. Recent findings have confirmed an important role for autophagy in both innate and adaptive immunity. The current study was undertaken to determine the efficacy of autophagy induction with Beclin-1, as a novel adjuvant system, in mice immunized with human papilloma virus (HPV) DNA vaccine.

METHODS

To determine whether autophagy induction with Beclin-1 enhances the efficacy of HPV DNA vaccine, female C57BL/6 mice were challenged with TC-1 tumor cells and were immunized three times at one-week intervals. Two weeks after the final immunization, the mice were sacrificed, and the antitumor effects were assessed by measurement of lymphocyte proliferation, cytotoxicity, cytokine production, and tumor regression.

RESULTS

Beclin-1 in combination with HPV-16 DNA vaccine encoding the E7 antigen induced a higher level of lymphocyte proliferation and cytotoxicity than the DNA vaccine alone. The novel combination increased the production of IFN-γ and highly inhibited tumor progression in comparison with DNA vaccine alone.

CONCLUSION

Administration of Beclin-1, as an autophagy inducer, with HPV DNA vaccine produces antitumor effects, providing an effective adjuvant for the induction of a strong antitumor immune response.

摘要

背景

开发一种有效的辅助系统以改进DNA疫苗的兴趣与日俱增。最近的研究结果证实了自噬在固有免疫和适应性免疫中均发挥重要作用。本研究旨在确定作为一种新型辅助系统的Beclin-1诱导自噬在用人乳头瘤病毒(HPV)DNA疫苗免疫的小鼠中的效果。

方法

为了确定Beclin-1诱导自噬是否增强HPV DNA疫苗的效果,用TC-1肿瘤细胞攻击雌性C57BL/6小鼠,并每隔一周免疫三次。末次免疫后两周,处死小鼠,并通过测量淋巴细胞增殖、细胞毒性、细胞因子产生和肿瘤消退来评估抗肿瘤效果。

结果

与单独的DNA疫苗相比,Beclin-1与编码E7抗原的HPV-16 DNA疫苗联合使用诱导了更高水平的淋巴细胞增殖和细胞毒性。与单独的DNA疫苗相比,这种新型联合用药增加了IFN-γ的产生,并高度抑制了肿瘤进展。

结论

将作为自噬诱导剂的Beclin-1与HPV DNA疫苗联合使用可产生抗肿瘤效果,为诱导强烈的抗肿瘤免疫反应提供了一种有效的辅助剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ce4/6800540/7553e92b0296/IBJ-23-388-g001.jpg

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