Preferential targeting of vesicular stomatitis virus to breast cancer cells
Preferential targeting of vesicular stomatitis virus to breast cancer cells
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DOI：
10.1016/j.virol.2004.06.048
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发表时间：
2004-12-05
期刊：
影响因子：
3.7
通讯作者：
Griffin, JA
中科院分区：
文献类型：
--
作者：
Bergman, I;Whitaker-Dowling, P;Griffin, JA
水泡性口炎病毒（VSV）是用于癌症治疗的候选病毒。我们创建了一种重组复制 VSV (rrVSV)，其表面蛋白发生改变，优先靶向乳腺癌细胞。 rrVSV 基因组包含源自辛德比斯病毒的单个糖蛋白 (gp) 基因。该基因表达嵌合的Sindbis E2结合gp和天然的Sindbis E1融合gp。嵌合 E2 结合 gp，称为 Sindbis-SCA-erbb2，经过修饰以减少其天然结合功能，并含有对人表皮生长因子受体 Her2/neu 蛋白 erbb2 具有特异性的单链抗体 (SCA)。这些病毒选择性地感染、复制并杀死表达 erbb2 的细胞。 rrVSV在SKBR3细胞（高度表达erbb2的人乳腺癌细胞系）上的滴度为3.1 x 10(7)/ml，而在143细胞（不表达erbb2的人骨肉瘤细胞系）上的滴度为73 x 10(5)/ml。 rrVSV 在 D2F2/E2 细胞（一种稳定转染表达人 erbb2 的小鼠乳腺癌细胞系）上的滴度为 2.46 x 10(6)/ml，而在不表达 erbb2 的亲代 D2F2 细胞上的滴度为 5 x 10(4)/ml。当对 erbb2 阴性细胞进行滴定时，涂有 Sindbis-SCA-erbb2 的非复制假型 VSV 具有
Vesicular stomatitis virus (VSV) is a candidate for development for cancer therapy. We created a recombinant replicating VSV (rrVSV) with an altered surface protein that targeted preferentially to breast cancer cells. The rrVSV genome contained a single glycoprotein (gp) gene derived from Sindbis virus. This gene expressed a chimeric Sindbis E2 binding gp and the native Sindbis El fusion gp. The chimeric E2 binding gp, called Sindbis-SCA-erbb2, was modified to reduce its native binding function and to contain a single chain antibody (SCA) with specificity for the human epidermal growth factor receptor Her2/neu protein, erbb2. These viruses selectively infected, replicated in and killed cells expressing erbb2. The titer of rrVSV on SKBR3 cells, a human breast cancer cell line which highly expresses erbb2 was 3.1 x 10(7)/ml compared with a titer of 73 x 10(5)/ml on 143 cells, a human osteosarcoma cell line which does not express erbb2. The titer of rrVSV on D2F2/E2 cells, a mouse mammary cancer cell line stably transfected to express human erbb2 was 2.46 x 10(6)/ml compared with a titer of 5 x 10(4)/ml on the parent D2F2 cells which do not express erbb2. When titered on erbb2-negative cells, non-replicating pseudotype VSV coated with Sindbis-SCA-erbb2 had