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FLT3L和粒细胞巨噬细胞集落刺激因子增强了HPV16 E6/E7疫苗的抗肿瘤和免疫效果。

FLT3L and granulocyte macrophage colony-stimulating factor enhance the anti-tumor and immune effects of an HPV16 E6/E7 vaccine.

作者信息

Ding Zhenzhen, Zhu Hua, Mo Laiming, Li Xiangyun, Xu Rui, Li Tian, Zhao Liang, Ren Yi, Xu Yunsheng, Ou Rongying

机构信息

Department of Dermatovenereology, Yuyao People's Hospital of Zhejiang Province, Yuyao, Zhejiang 315400, China.

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

出版信息

Aging (Albany NY). 2019 Dec 24;11(24):11893-11904. doi: 10.18632/aging.102494.

Abstract

HPV16 infections promote the development and progression of cervical cancer. We investigated Fms-like Tyrosine Kinase 3 Ligand and granulocyte macrophage colony-stimulating factor as new adjuvants to an HPV16 vaccine. C57BL/6 mice were immunized by intramuscular injections of HPV16 E6/E7 plasmids every two weeks, three times in all. An imaging system was used to observe tumor growth and metastasis. Pathological changes to the heart, liver, spleen, lungs, brain and kidneys were recorded, and the survival rate of the mice was determined. The constructed HPV16 E6/E7 vaccine had no notable side effects in terms of physiological or biochemical indexes. Fms-like Tyrosine Kinase 3 Ligand and granulocyte macrophage colony-stimulating factor increased the inhibitory effects of the HPV16 E6/E7 vaccine on tumor growth and metastasis The HPV16 E6/E7 vaccine enhanced the survival of mice and increased their serum-specific antibody and interferon-γ levels. Fms-like Tyrosine Kinase 3 Ligand and granulocyte macrophage colony-stimulating factor augmented these effects. In a cytotoxic lymphocyte killing test, Fms-like Tyrosine Kinase 3 Ligand and granulocyte macrophage colony-stimulating factor improved the ability of splenic lymphocytes from HPV16 E6/E7-vaccinated mice to kill B16 cells. As Fms-like Tyrosine Kinase 3 Ligand and granulocyte macrophage colony-stimulating factor enhanced the anti-tumor and immune effects of the HPV16 vaccine, these adjuvants should be considered for the treatment of cervical cancer.

摘要

人乳头瘤病毒16型(HPV16)感染会促进宫颈癌的发生和发展。我们研究了Fms样酪氨酸激酶3配体(Flt3L)和粒细胞巨噬细胞集落刺激因子(GM-CSF)作为HPV16疫苗新佐剂的作用。通过肌肉注射HPV16 E6/E7质粒,每两周对C57BL/6小鼠进行一次免疫,共免疫三次。使用成像系统观察肿瘤生长和转移情况。记录心脏、肝脏、脾脏、肺、脑和肾脏的病理变化,并测定小鼠的存活率。构建的HPV16 E6/E7疫苗在生理和生化指标方面没有明显的副作用。Flt3L和GM-CSF增强了HPV16 E6/E7疫苗对肿瘤生长和转移的抑制作用。HPV16 E6/E7疫苗提高了小鼠的存活率,并增加了它们的血清特异性抗体和干扰素-γ水平。Flt3L和GM-CSF增强了这些作用。在细胞毒性淋巴细胞杀伤试验中,Flt3L和GM-CSF提高了接种HPV16 E6/E7疫苗小鼠的脾淋巴细胞杀伤B16细胞的能力。由于Flt3L和GM-CSF增强了HPV16疫苗的抗肿瘤和免疫效果,这些佐剂可考虑用于宫颈癌的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cc2/6949056/891ee65827b8/aging-11-102494-g001.jpg

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