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拉沙病毒-水泡性口炎病毒嵌合病毒通过直接溶瘤作用和引发抗肿瘤反应靶向并摧毁人类和小鼠卵巢癌细胞。

Lassa-VSV chimeric virus targets and destroys human and mouse ovarian cancer by direct oncolytic action and by initiating an anti-tumor response.

机构信息

Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.

Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT, USA.

出版信息

Virology. 2021 Mar;555:44-55. doi: 10.1016/j.virol.2020.10.009. Epub 2020 Nov 12.

Abstract

Ovarian cancer is the third most common female cancer, with poor survival in later stages of metastatic spread. We test a chimeric virus consisting of genes from Lassa and vesicular stomatitis viruses, LASV-VSV; the native VSV glycoprotein is replaced by the Lassa glycoprotein, greatly reducing neurotropism. Human ovarian cancer cells in immunocompromised nude mice were lethal in controls. Chemotherapeutic paclitaxel and cisplatin showed modest cancer inhibition and survival extension. In contrast, a single intraperitoneal injection of LASV-VSV selectively infected and killed ovarian cancer cells, generating long-term survival. Mice with human ovarian cancer cells in brain showed rapid deterioration; LASV-VSV microinjection into brain blocked cancer growth, and generated long-term survival. Treatment of immunocompetent mice with infected mouse ovarian cancer cells blocked growth of non-infected ovarian cancer cells peritoneally and in brain. These results suggest LASV-VSV is a viable candidate for further study and may be of use in the treatment of ovarian cancer.

摘要

卵巢癌是第三大常见女性癌症,在转移性扩散的晚期生存状况较差。我们测试了一种嵌合病毒,由拉萨病毒和水疱性口炎病毒的基因组成,即 LASV-VSV;其天然 VSV 糖蛋白被拉萨糖蛋白取代,大大降低了神经嗜性。在免疫功能低下的裸鼠中,人类卵巢癌细胞在对照中是致命的。化疗药物紫杉醇和顺铂显示出适度的癌症抑制和生存延长。相比之下,单次腹腔内注射 LASV-VSV 可选择性感染和杀死卵巢癌细胞,从而延长生存时间。患有脑内人类卵巢癌细胞的小鼠迅速恶化;LASV-VSV 脑内微注射可阻止癌症生长,并产生长期生存。用感染的小鼠卵巢癌细胞治疗免疫功能正常的小鼠可阻止腹腔和脑部非感染卵巢癌细胞的生长。这些结果表明 LASV-VSV 是进一步研究的可行候选者,可能对卵巢癌的治疗有用。

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本文引用的文献

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Diagnosis and Treatment of Ovarian Cancer.卵巢癌的诊断与治疗
Hematol Oncol Clin North Am. 2018 Dec;32(6):943-964. doi: 10.1016/j.hoc.2018.07.010.

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