Kochneva G V, Sivolobova G F, Iudina K V, Babkin I V, Chumakov P M, Netesov S V
Mol Gen Mikrobiol Virusol. 2012(1):8-15.
The latest data on selection and construction of poxviruses capable of specifically lysing tumor cells of different genesis, inducing antitumor immunity and apoptosis of malignant cells are discussed. The review concerns several directions: virus attenuation, insertion of immunomodulatory protein genes, and anti-tumor protein genes. Thymidine kinase and viral growth factor genes make the greatest contribution to the virus attenuation as their inactivation results in the virus inability to replicate in non-dividing cells, thereby contributing to increased selectivity with respect to tumor cells. Among the immunomodulatory proteins, interleukins 2, 12, and granulocyte-macrophage colony-stimulating factor proved to be most promising for oncolytic virotherapy. An attempt to use p53 protein gene expressed by vaccinia virus for addressed apoptosis of tumor cells was reported. The use of the double and triple viral recombinants carrying genes of multidirectional action seems to be most promising. Encouraging results were obtained using vaccinia virus in the oncotherapy with prodrugs and angiogenesis inhibitors. At present, two poxviral strains are undergoing Phase III clinical trials as anti-tumor preparations in the USA.
讨论了有关选择和构建能够特异性裂解不同起源肿瘤细胞、诱导抗肿瘤免疫及恶性细胞凋亡的痘病毒的最新数据。综述涉及几个方向：病毒减毒、免疫调节蛋白基因的插入以及抗肿瘤蛋白基因。胸苷激酶和病毒生长因子基因对病毒减毒贡献最大，因为它们的失活导致病毒无法在非分裂细胞中复制，从而提高了对肿瘤细胞的选择性。在免疫调节蛋白中，白细胞介素2、12和粒细胞-巨噬细胞集落刺激因子被证明在溶瘤病毒疗法中最具前景。有报道尝试使用痘苗病毒表达的p53蛋白基因来靶向肿瘤细胞凋亡。使用携带多向作用基因的双重组和三重重组病毒似乎最具前景。在与前体药物和血管生成抑制剂联合进行肿瘤治疗中使用痘苗病毒取得了令人鼓舞的结果。目前，在美国有两种痘病毒株正在作为抗肿瘤制剂进行III期临床试验。
