Immune safety of a novel oncolytic mutant M1 after administration In Vivo

Immune safety of a novel oncolytic mutant M1 after administration In Vivo
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新型溶瘤突变体 M1 体内给药后的免疫安全性

DOI:
10.1007/s11596-012-0089-4
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发表时间:
2012-08
影响因子:
--
通讯作者:
Cao, Yang
Cao, Yang
中科院分区:
生物4区
文献类型:
--
作者:
Jiang, Lijun;Zhou, Xiaoxi;Li, Qinlu;Yu, Fei;Huang, Liang;Ma, Quanfu;Zhou, Jianfeng;Cao, Yang

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这项研究的目的是评估一种新型的溶瘤腺病毒突变体M1与免疫抑制剂联合使用的安全性和有效性。通过静脉或腹膜后注射纯化的M1建立动物模型。在不同的时间点,从小鼠身上取血进行肝肾功能检测。取肝脏进行光镜检查,观察病理变化。免疫组织化学方法检测重组腺病毒在肝脏中的表达。还分析了淋巴细胞向肝脏的募集和腺病毒特异性T细胞的激活。没有观察到全身毒性的迹象,但在给予M1后观察到ALT和Scr的一过性升高。显微镜检查显示肝脏有轻微的炎症反应。与静脉注射相比,腹膜后注射后,腺病毒蛋白的表达水平更高。环孢素A联合治疗可改善肝肾功能障碍,增加肝组织中腺病毒的浓度。体内使用新型溶瘤腺病毒突变体M1是安全的,M1与免疫抑制剂联合使用能够增强M1的有效性和安全性。
The aim of this study was to evaluate the safety and efficiency of a novel, oncolytic adenovirus mutant M1 administered in conjunction with immunosuppressive agents. Animal models were established by administering purified M1 either intravenously or retroperitoneally. At different time points, blood samples were taken from the mice for testing of liver and renal function. Microscopic examination of the liver was performed to observe pathological changes. Immunohistochemical analyses were used to evaluate the expression of the adenovirus in the liver. Lymphocyte recruitment to the liver and the activation of adenovirus specific T cells were also analyzed. No signs of general toxicity were observed, but transient increases in ALT and Scr were observed following the administration of M1. Microscopic examination revealed a mild inflammatory response in the liver. Compared to intravenous injection, higher expression levels of adenoviral proteins were observed after retroperitoneal injection. Combined treatment with cyclosporine A resolved the liver and kidney dysfunction and increased the concentration of the adenovirus in the liver. The use of the novel oncolytic adenovirus mutant M1 in vivo is safe, and the combined administration of M1 with immunosuppressive agents was able to enhance the effectiveness and safety profile of M1.
DOI: 10.1089/hum.1997.8.10-1195
发表时间: 1997-07
期刊: Human gene therapy
影响因子: 4.2
作者:
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通讯作者: Deborah E. Sullivan;S. Dash;Hong Du;Naoki Hiramatsu;Faruk Aydin;Jay K. Kolls;James Blanchard;Gary B. Baskin;Michael A. Gerber
DOI: 10.1177/154405910408300905
发表时间: 2004-09-01
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DOI: 10.1089/10430340152712692
发表时间: 2002-01-01
期刊: HUMAN GENE THERAPY
影响因子: 4.2
作者:
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DOI: 10.1007/s11596-011-0148-2
发表时间: 2011-02
期刊: Journal of Huazhong University of Science and Technology [Medical Sciences]
影响因子: --
作者:
Quan Wei;Zhao-yu Liu;Yu-jie Fei;Danyue Peng;H. Zuo;Xiaolin Huang;Z. Liu;Xin A. Zhang
通讯作者: Quan Wei;Zhao-yu Liu;Yu-jie Fei;Danyue Peng;H. Zuo;Xiaolin Huang;Z. Liu;Xin A. Zhang
DOI: 10.1038/sj.gt.3302364
发表时间: 2004-10-01
期刊: GENE THERAPY
影响因子: 5.1
作者:
Bessis, N;GarciaCozar, FJ;Boissier, MC
通讯作者: Boissier, MC