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Flt3L和粒细胞-巨噬细胞集落刺激因子通过增强免疫反应来提高HPV16/18疫苗的抗肿瘤效果。

Flt3L and GM-CSF enhance anti-tumor effect of HPV16/18 vaccine via increasing immune response.

作者信息

Liu Yu, Zhu Haiyan, Mo Laiming, Xu Rui, Li Xiangyun, Li Tian, Zhao Liang, Ren Yi, Ou Rongying, Xu Yunsheng

机构信息

Department of Dermatovenereology, The Seventh Affiliated Hospital, Sun Yat-Sen University Shenzhen 518107, Guangdong, China.

Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325000, Zhejiang, China.

出版信息

Am J Transl Res. 2020 Oct 15;12(10):6027-6042. eCollection 2020.

Abstract

OBJECTIVES

Cervical cancer is the second leading cause of cancer death in women, which is closely related to persistent infection with high-risk Human papillomavirus (HPV). Therefore, it is important to develop new adjuvants for HPV vaccines. This research aimed to establish two new adjuvants which can enhance the immune effect of vaccines.

MATERIALS AND METHODS

C57BL/6 mice were divided into 5 groups and immunized by intramuscular injection of plasmid once every 2 weeks, three times in all. The growth and metastasis of tumors in mice was observed by imaging system (IVIS). Then, the mice were sacrificed and the pathological changes of organs were observed. In addition, the lymphocyte suspension was used for CLT killing test. IFN-γ level and the number of splenocytes which secrete IFN-γ were detected. Additionally, the specific antibody level of HPV16/18 E6 E7 L1 L2 was also detected.

RESULTS

The constructed nucleic acid vaccines had no significant effect on both the physiological and biochemical indexes, while it significantly increased the survival period and survival rate of mice. Flt3L and GM-CSF enhanced the immune effect of HPV16/18 vaccine via increasing the specific antibodies and IFN-γ cytokines.

CONCLUSIONS

These data suggested that Flt3L and GM-CSF enhanced the anti-tumor effect of vaccines via increasing immune response. Thereby, our findings may hope to provide new perspective for the treatment of cervical cancer.

摘要

目的

宫颈癌是女性癌症死亡的第二大主要原因,与高危型人乳头瘤病毒(HPV)的持续感染密切相关。因此,开发HPV疫苗的新型佐剂很重要。本研究旨在建立两种可增强疫苗免疫效果的新型佐剂。

材料与方法

将C57BL/6小鼠分为5组,每2周肌肉注射质粒免疫一次,共免疫3次。通过成像系统(IVIS)观察小鼠肿瘤的生长和转移情况。然后,处死小鼠,观察器官的病理变化。此外,将淋巴细胞悬液用于细胞毒性淋巴细胞(CLT)杀伤试验。检测干扰素-γ(IFN-γ)水平及分泌IFN-γ的脾细胞数量。另外,还检测了HPV16/18 E6 E7 L1 L2的特异性抗体水平。

结果

构建的核酸疫苗对生理生化指标均无显著影响,但显著延长了小鼠的生存期并提高了生存率。Flt3L和粒细胞-巨噬细胞集落刺激因子(GM-CSF)通过增加特异性抗体和IFN-γ细胞因子增强了HPV16/18疫苗的免疫效果。

结论

这些数据表明,Flt3L和GM-CSF通过增强免疫反应提高了疫苗的抗肿瘤效果。因此,我们的研究结果有望为宫颈癌的治疗提供新的视角。

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