Comparison of safety, delivery, and efficacy of two oncolytic herpes viruses (G207 and NV1020) for peritoneal cancer
Comparison of safety, delivery, and efficacy of two oncolytic herpes viruses (G207 and NV1020) for peritoneal cancer
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DOI：
10.1038/sj.cgt.7700510
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发表时间：
2002-11-01
影响因子：
6.4
通讯作者：
Fong, YM
中科院分区：
文献类型：
--
作者：
Bennett, JJ;Delman, KA;Fong, YM
G207和NV1020是两种具有复制能力的多突变单纯性溶瘤病毒，目前的研究评估了它们在胃癌治疗中的抗癌作用。伽马(1)34.5基因的缺失和ICP6(核糖核苷酸还原酶)的失活使G207能够选择性地在肿瘤细胞内复制。NV1020是另一种具有HSV结合区缺失的减毒重组疱疹病毒，仅缺失一个拷贝的Gamma(1)34.5基因，且ICP6基因完整。在体外，G207和NV1020都有效地感染、复制和杀死了人胃癌细胞，其中NV1020在较低浓度的病毒下更有效。在小鼠腹膜播散性胃癌异种移植模型中，NV1020和G207在给药时均可减轻肿瘤负担。在更高的剂量。当病毒剂量降低或晚期肿瘤治疗时，I.P.NV1020优于I.P.G207。体外病毒复制和细胞毒性可预测体内的抗肿瘤反应。静脉注射G207或NV1020均未能减轻肿瘤负担，表明区域治疗作为分区治疗恶性肿瘤的重要性。这两种药物在动物身上使用都是安全的，在小鼠组织上进行的免疫组织化学显示，选择性的病毒靶向肿瘤。使用基因工程HSV进行溶瘤治疗是治疗腹膜恶性肿瘤的一种很有前途的策略。
G207 and NV1020 are two replication-competent, multi mutant oncolytic herpes simplex viruses evaluated in the current studies for their anticancer effects in the treatment of gastric cancer. Deletion of both gamma(1)34.5 genes and inactivation of ICP6 (ribonucleotide reductase) allows G207 to selectively replicate within tumor cells. NV1020 is another attenuated recombinant herpes virus with deletions of the HSV joint region, with deletion of only one copy of the gamma(1)34.5 gene, and with the ICP6 gene intact. In vitro, both G207 and NV1020 effectively infected, replicated, and killed human gastric cancer cells, with NV1020 being more effective at lower concentrations of virus. In a murine xenograft model of peritoneally disseminated gastric cancer, both NV1020 and G207 reduced tumor burden when given intraperitoneally (i.p.) at higher doses. When viral doses were lowered or when advanced tumor was treated, i.p. NV1020 was superior to i.p. G207. In vitro viral replication and cytotoxicity predicted the in vivo antitumor response. Intravenous delivery of either G207 or NV1020 failed to reduce tumor burden, demonstrating the importance of regional therapy as treatment for compartmentalized malignancy. Both agents were safe for use in animals, and immunohistochemistry performed on mouse tissue revealed selective viral targeting of tumor. Oncolytic therapy using genetically engineered HSVs represents a promising strategy for peritoneal malignancies.