In vivo antitumor activity of Sindbis viral vectors.
In vivo antitumor activity of Sindbis viral vectors.
复制标题
辛德毕斯病毒载体的体内抗肿瘤活性。
DOI：
10.1093/jnci/94.23.1790
复制
发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Meruelo,Daniel
中科院分区：
文献类型：
--
作者：
Tseng,Jen-Chieh;Levin,Brandi;Hirano,Tadamichi;Yee,Herman;Pampeno,Christine;Meruelo,Daniel
Background:Sindbis virus, a blood-borne virus transmitted by mosquitoes, has been used as a vector to efficiently express exogenous genesin vitroandin vivoand to induce apoptosis. Because Sindbis virus infects mammalian cells by interacting with the high-affinity laminin receptors, which are expressed at higher levels in several human cancers than in normal cells, we determined whether a Sindbis viral vector could be used to target cancersin vivo.Methods:C.B-17-SCID mice with established xenografts were given daily intraperitoneal injections of the Sindbis viral vector SinRep/LacZ containing the bacterial β-galactosidase gene. Control mice were untreated or received injections with phosphate-buffered saline. Tumor size was measured daily. Expression of β-galactosidase and Factor VIII (a marker for endothelial cells) was determined by immunohistochemical staining of tumor sections. Apoptosis was analyzed by TUNEL (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP nick end labeling) staining. C.B-17-SCID beige mice, which lack natural killer (NK) cells, were used to assess the importance of NK cells in antitumor efficacy of Sindbis viral vectors.Results:Tumors from mice treated with SinRep/LacZ were statistically significantly smaller than tumors from control mice. This effect was observed for tumor xenografts derived from BHK (kidney, hamster), LS174T (colon, human), HT29 (colon, human), and CFPAC (pancreas, human) cells. Expression of β-galactosidase co-localized with that of Factor VIII in tumor sections. Tumors from SinRep/LacZ-treated mice contained more apoptotic cells than tumors from control mice. Complete tumor regression was observed in three of five C.B-17-SCID mice but in none of five C.B-17-SCID beige mice treated with SinRep/LacZ.Conclusion:Sindbis viral vectors efficiently targeted tumorsin vivo, were apparently delivered through the circulation, and were more effective in the presence of NK cells.
