Vasileva Natalia, Ageenko Alisa, Dmitrieva Maria, Nushtaeva Anna, Mishinov Sergey, Kochneva Galina, Richter Vladimir, Kuligina Elena
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Akad. Lavrentiev Ave. 8, 630090 Novosibirsk, Russia.
LLC "Oncostar", R&D Department, Ingenernaya Street 23, 630090 Novosibirsk, Russia.
Life (Basel). 2021 Oct 14;11(10):1084. doi: 10.3390/life11101084.
Glioblastoma is one of the most aggressive brain tumors. Given the poor prognosis of this disease, novel methods for glioblastoma treatment are needed. Virotherapy is one of the most actively developed approaches for cancer therapy today. VV-GMCSF-Lact is a recombinant vaccinia virus with deletions of the viral thymidine kinase and growth factor genes and insertions of the granulocyte-macrophage colony-stimulating factor and oncotoxic protein lactaptin genes. The virus has high cytotoxic activity against human cancer cells of various histogenesis and antitumor efficacy against breast cancer. In this work, we show VV-GMCSF-Lact to be a promising therapeutic agent for glioblastoma treatment. VV-GMCSF-Lact effectively decreases the viability of glioblastoma cells of both immortalized and patient-derived cultures in vitro, crosses the blood-brain barrier, selectively replicates into orthotopically transplanted human glioblastoma when intravenously injected, and inhibits glioblastoma xenograft and metastasis growth when injected intratumorally.
胶质母细胞瘤是最具侵袭性的脑肿瘤之一。鉴于这种疾病预后较差,需要新的胶质母细胞瘤治疗方法。病毒疗法是当今癌症治疗中最积极开发的方法之一。VV-GMCSF-Lact是一种重组痘苗病毒,其病毒胸苷激酶和生长因子基因缺失,粒细胞-巨噬细胞集落刺激因子和肿瘤毒性蛋白乳凝集素基因插入。该病毒对各种组织发生的人类癌细胞具有高细胞毒性活性,对乳腺癌具有抗肿瘤功效。在这项工作中,我们表明VV-GMCSF-Lact是一种有前途的胶质母细胞瘤治疗药物。VV-GMCSF-Lact在体外有效降低永生化和患者来源培养物的胶质母细胞瘤细胞的活力,穿过血脑屏障,静脉注射时选择性地在原位移植的人类胶质母细胞瘤中复制,瘤内注射时抑制胶质母细胞瘤异种移植和转移生长。