Growth inhibition of different human colorectal cancer xenografts after a single intravenous injection of oncolytic vaccinia virus GLV-1h68.
Growth inhibition of different human colorectal cancer xenografts after a single intravenous injection of oncolytic vaccinia virus GLV-1h68.
复制标题
DOI：
10.1186/1479-5876-11-79
复制
发表时间：
2013-03-26
影响因子：
7.4
通讯作者：
Szalay AA
中科院分区：
文献类型：
--
作者：
Ehrig K;Kilinc MO;Chen NG;Stritzker J;Buckel L;Zhang Q;Szalay AA
尽管早期结直肠癌有有效的治疗方案，但晚期结直肠癌的治疗方案通常无效，因此需要改进。利用具有复制能力的牛痘病毒（VACV）株进行溶瘤病毒治疗是治疗多种人类癌症的一种有前景的新策略。在细胞培养和皮下异种移植肿瘤模型中分析了复制活性牛痘病毒GLV-1h68的溶瘤效果。在这项研究中，我们首次证明了具有复制能力的重组VACV GLV-1h68能够有效地感染、复制并随后裂解来自所有四个疾病阶段患者的各种人类结直肠癌系（Colo 205、HCT-15、HCT-116、HT-29和SW-620）。此外，在胸腺裸鼠的肿瘤异种移植模型中，单次静脉注射GLV-1h68可显著抑制两种不同的人类结直肠细胞系肿瘤（Duke’s a型HCT-116和Duke’s c型sw620）的肿瘤生长，与未治疗的小鼠相比，可显著提高生存率。病毒标记基因ruc-gfp的表达允许在细胞培养物和小鼠中实时分析病毒感染。GLV-1h68治疗在所有动物中耐受性良好，病毒复制仅限于肿瘤。与未处理的对照组相比，GLV-1h68处理引起小鼠免疫相关抗原如IFN-γ、IP-10、MCP-1、MCP-3、MCP-5、RANTES和TNF-γ的显著上调，并且肿瘤中巨噬细胞和NK细胞的浸润量增加。在这些研究中观察到的对结直肠癌细胞的抗肿瘤活性是GLV-1h68直接病毒溶瘤和炎症介导的先天免疫反应的结果。这种治疗效果发生在肿瘤中，与细胞来自的疾病阶段无关。因此，重组痘苗病毒GLV-1h68具有独立于进展阶段治疗结直肠癌的潜力。
Despite availability of efficient treatment regimens for early stage colorectal cancer, treatment regimens for late stage colorectal cancer are generally not effective and thus need improvement. Oncolytic virotherapy using replication-competent vaccinia virus (VACV) strains is a promising new strategy for therapy of a variety of human cancers. Oncolytic efficacy of replication-competent vaccinia virus GLV-1h68 was analyzed in both, cell cultures and subcutaneous xenograft tumor models. In this study we demonstrated for the first time that the replication-competent recombinant VACV GLV-1h68 efficiently infected, replicated in, and subsequently lysed various human colorectal cancer lines (Colo 205, HCT-15, HCT-116, HT-29, and SW-620) derived from patients at all four stages of disease. Additionally, in tumor xenograft models in athymic nude mice, a single injection of intravenously administered GLV-1h68 significantly inhibited tumor growth of two different human colorectal cell line tumors (Duke’s type A-stage HCT-116 and Duke’s type C-stage SW-620), significantly improving survival compared to untreated mice. Expression of the viral marker gene ruc-gfp allowed for real-time analysis of the virus infection in cell cultures and in mice. GLV-1h68 treatment was well-tolerated in all animals and viral replication was confined to the tumor. GLV-1h68 treatment elicited a significant up-regulation of murine immune-related antigens like IFN-γ, IP-10, MCP-1, MCP-3, MCP-5, RANTES and TNF-γ and a greater infiltration of macrophages and NK cells in tumors as compared to untreated controls. The anti-tumor activity observed against colorectal cancer cells in these studies was a result of direct viral oncolysis by GLV-1h68 and inflammation-mediated innate immune responses. The therapeutic effects occurred in tumors regardless of the stage of disease from which the cells were derived. Thus, the recombinant vaccinia virus GLV-1h68 has the potential to treat colorectal cancers independently of the stage of progression.
登录
查看更多内容
影响因子：
4.8
作者：
Israelsson S;Jonsson N;Gullberg M;Lindberg AM
通讯作者：
Lindberg AM
影响因子：
3.8
作者：
Lin, Shu-Fu;Yu, Zhenkun;Wong, Richard J.
通讯作者：
Wong, Richard J.
影响因子：
5.8
作者：
Lin, Shu-Fu;Price, Daniel L.;Wong, Richard J.
通讯作者：
Wong, Richard J.
影响因子：
3.7
作者：
Silver J;Mei YF
通讯作者：
Mei YF
影响因子：
11.5
作者：
Advani, Sunil J.;Buckel, Lisa;Szalay, Aladar A.
通讯作者：
Szalay, Aladar A.