Treatment of implanted mammary tumors with recombinant vesicular stomatitis virus targeted to Her2/neu
Treatment of implanted mammary tumors with recombinant vesicular stomatitis virus targeted to Her2/neu
复制标题
DOI：
10.1002/ijc.22680
复制
发表时间：
2007-07-15
影响因子：
6.4
通讯作者：
Whitaker-Dowling, Patricia
中科院分区：
文献类型：
--
作者：
Bergman, Ira;Griffin, Judith A.;Whitaker-Dowling, Patricia
水泡性口炎病毒（VSV）正在开发用于癌症治疗。我们已经创建了重组复制VSV（rrVSV），其靶向表达Her 2/neu的乳腺癌细胞并表达小鼠GM-CSF。我们现在测试了这种rrVSV在治疗D2 F2/E2细胞的腹膜肿瘤植入物中的功效，D2 F2/E2细胞是一种BALB/c小鼠乳腺肿瘤细胞系，其被稳定转染以表达Her 2/neu。在肿瘤植入后1天，用2 × 108感染剂量的rrVSV或条件培养基（CM）处理小鼠。所有对照组动物均出现巨大腹膜肿瘤，中位生存期为16天。10只rrVSV处理的小鼠中有9只长期存活，没有肿瘤的迹象。rrVSV在处理不表达Her 2/neu的亲本D2 F2细胞的植入物中具有低得多的功效。中位生存期为13.5天，在CM治疗的小鼠和21天，在rrVSV治疗。rrVSV治疗组中有1例长期存活。rrVSV处理的动物均未显示病毒毒性的证据。当首先用D2 F2/E2再用D2 F2细胞再激发时，7个长期存活者中的3个没有发生肿瘤。成功的治疗和对再激发的抵抗都是T细胞依赖性的。这些研究表明，靶向的rrVSV消除了表达Her 2/neu的肿瘤的腹膜植入物，并引发了抗肿瘤T细胞免疫应答。(C)2007 Wiley-Liss，Inc.
Vesicular stomatitis virus (VSV) is being developed for cancer therapy. We have created a recombinant replicating VSV (rrVSV) that targeted to Her2/neu expressing breast cancer cells and expresses mouse GM-CSF. We now tested the efficacy of this rrVSV in the treatment of peritoneal tumor implants of D2F2/E2 cells, a BALB/c mouse mammary tumor cell line, which was stably transfected to express Her2/neu. Mice were treated I day following tumor implantation with either 2 x 10(8) infectious doses rrVSV or conditioned media (CM). All control animals developed massive peritoneal tumor with a median survival of 16 days. Nine of 10 rrVSV treated mice survived long term with no evidence of tumor. rrVSV had much less efficacy in treating implants of the parent D2F2 cells that did not express Her2/neu. The median survival was 13.5 days in mice treated with CM and 21 days in those treated with rrVSV. There was one long term survivor in the rrVSV treated group. None of the rrVSV treated animals showed evidence of viral toxicity. Three of 7 long term survivors did not develop tumor when rechallenged first with D2F2/E2 and then with D2F2 cells. Both successful therapy and resistance to rechallenge were T-cell dependent. These studies demonstrate that targeted rrVSV eliminated peritoneal implants of Her2/neu expressing tumor and elicited an anti-tumor T-cell immunologic response. (C) 2007 Wiley-Liss, Inc.