Suppr超能文献

单纯疱疹溶瘤病毒的联合血管递送和扩增子介导的细胞因子基因转移是实验性肝癌的有效治疗方法。

Combination vascular delivery of herpes simplex oncolytic viruses and amplicon mediated cytokine gene transfer is effective therapy for experimental liver cancer.

作者信息

Zager J S, Delman K A, Malhotra S, Ebright M I, Bennett J J, Kates T, Halterman M, Federoff H, Fong Y

机构信息

Department of Surgery, Hepatobiliary Division, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

出版信息

Mol Med. 2001 Aug;7(8):561-8.

Abstract

BACKGROUND

Herpes simplex type I (HSV)-based vectors have been used experimentally for suicide gene therapy, immunomodulatory gene delivery, and direct oncolytic therapy. The current study utilizes the novel concept of regional delivery of an oncolytic virus in combination with or serving as the helper virus for packaging herpes-based amplicon vectors carrying a cytokine transgene, with the goal of identifying if this combination is more efficacious than either modality alone.

MATERIALS AND METHODS

A replication competent oncolytic HSV (G207) and a replication incompetent HSV amplicon carrying the gene for the immunomodulatory cytokine IL-2 (HSV-IL2) were tested in murine syngeneic colorectal carcinoma and in rat hepatocellular carcinoma models. Liver tumors were treated with vascular delivery of (1) phosphate-buffered saline (PBS), (2) G207, (3) HSV-IL2, (4) G207 and HSV-IL2 mixed in combination (mG207/HSV- IL2), and (5) G207 as the helper virus for packaging the construct HSV-IL2 (pG207/HSV-IL2).

RESULTS

Tumor burden was significantly reduced in all treatment groups in both rats and mice treated with high-dose G207, HSV-IL2, or both (p < 0.02). When a low dose of virus was used in mice, anti-tumor efficacy was improved by use of G207 and HSV-IL2 in combination or with HSV-IL2 packaged by G207 (p < 0.001). This improvement was abolished when CD4(+) and CD8(+) lymphocytes were depleted, implying that the enhanced anti-tumor response to low-dose combined therapy is immune mediated.

CONCLUSIONS

Vascular regional delivery of oncolytic and amplicon HSV vectors can be used to induce improved anti-tumor efficacy by combining oncolytic and immunostimulatory strategies.

摘要

背景

基于I型单纯疱疹病毒(HSV)的载体已被用于自杀基因治疗、免疫调节基因递送和直接溶瘤治疗的实验研究。本研究采用了一种新的概念,即区域性递送溶瘤病毒,并将其与携带细胞因子转基因的基于疱疹病毒的扩增载体联合使用或作为包装辅助病毒,目的是确定这种联合使用是否比单独使用任何一种方式更有效。

材料与方法

在小鼠同基因结直肠癌和大鼠肝细胞癌模型中,对一种具有复制能力的溶瘤HSV(G207)和一种携带免疫调节细胞因子IL-2基因的无复制能力的HSV扩增载体(HSV-IL2)进行了测试。通过血管注射对肝肿瘤进行治疗,治疗药物包括:(1)磷酸盐缓冲盐水(PBS);(2)G207;(3)HSV-IL2;(4)G207和HSV-IL2混合制剂(mG207/HSV-IL2);(5)作为包装构建体HSV-IL2的辅助病毒的G207(pG207/HSV-IL2)。

结果

在接受高剂量G207、HSV-IL2或两者治疗的大鼠和小鼠中,所有治疗组的肿瘤负荷均显著降低(p<0.02)。当在小鼠中使用低剂量病毒时,联合使用G207和HSV-IL2或使用由G207包装的HSV-IL2可提高抗肿瘤疗效(p<0.001)。当CD4(+)和CD8(+)淋巴细胞被清除时,这种改善作用消失,这意味着低剂量联合治疗增强的抗肿瘤反应是由免疫介导的。

结论

通过血管区域递送溶瘤和扩增性HSV载体,联合溶瘤和免疫刺激策略可提高抗肿瘤疗效。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验