Oncolytic Immunotherapy for Bladder Cancer Using Coxsackie A21 Virus.
Oncolytic Immunotherapy for Bladder Cancer Using Coxsackie A21 Virus.
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DOI：
10.1016/j.omto.2018.02.001
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发表时间：
2018-06-29
期刊：
影响因子：
--
通讯作者：
Pandha H
中科院分区：
文献类型：
--
作者：
Annels NE;Arif M;Simpson GR;Denyer M;Moller-Levet C;Mansfield D;Butler R;Shafren D;Au G;Knowles M;Harrington K;Vile R;Melcher A;Pandha H
作为一个临床环境，其中局部活生物治疗已经很好地建立，非肌肉浸润性膀胱癌（NMIBC）提出了有趣的机会，溶瘤病毒治疗。柯萨奇病毒A21（Coxsackievirus A21，CVA 21）是一种以细胞间粘附分子-1（ICAM-1）为靶点的新型免疫抑制病毒。这项研究调查了CVA 21诱导的细胞毒性在一组人膀胱癌细胞系，揭示了一系列的敏感性，主要与病毒受体ICAM-1的表达。CVA 21与低剂量丝裂霉素-C的组合通过增加ICAM-1的表面表达水平来增强CVA 21病毒复制和溶瘤作用。使用NMIBC的300 μm精密切片进一步证实了这一点，其中病毒蛋白表达水平和细胞凋亡诱导水平在预先暴露于丝裂霉素C时增强。鉴于垂死癌细胞的免疫原性对于触发肿瘤特异性应答和长期治疗成功的重要性，研究了CVA 21诱导免疫原性细胞死亡的能力。CVA 21在膀胱癌细胞系中诱导免疫原性细胞凋亡，如通过免疫原性细胞死亡（ICD）决定因子钙网蛋白的表达和HMGB-1释放以及在用经历CVA 21诱导的ICD的MB 49细胞接种后在同基因小鼠中排斥MB 49肿瘤的能力所证明的。这种CVA 21免疫疗法可以为膀胱癌的治疗提供一种潜在的毒性更小，更有效的选择。
As a clinical setting in which local live biological therapy is already well established, non-muscle invasive bladder cancer (NMIBC) presents intriguing opportunities for oncolytic virotherapy. Coxsackievirus A21 (CVA21) is a novel intercellular adhesion molecule-1 (ICAM-1)-targeted immunotherapeutic virus. This study investigated CVA21-induced cytotoxicity in a panel of human bladder cancer cell lines, revealing a range of sensitivities largely correlating with expression of the viral receptor ICAM-1. CVA21 in combination with low doses of mitomycin-C enhanced CVA21 viral replication and oncolysis by increasing surface expression levels of ICAM-1. This was further confirmed using 300-μm precision slices of NMIBC where levels of virus protein expression and induction of apoptosis were enhanced with prior exposure to mitomycin-C. Given the importance of the immunogenicity of dying cancer cells for triggering tumor-specific responses and long-term therapeutic success, the ability of CVA21 to induce immunogenic cell death was investigated. CVA21 induced immunogenic apoptosis in bladder cancer cell lines, as evidenced by expression of the immunogenic cell death (ICD) determinant calreticulin, and HMGB-1 release and the ability to reject MB49 tumors in syngeneic mice after vaccination with MB49 cells undergoing CVA21 induced ICD. Such CVA21 immunotherapy could offer a potentially less toxic, more effective option for the treatment of bladder cancer.
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宇宙（癌症中的体细胞突变目录）数据库和网站。
影响因子：
8.8
作者：
Bamford, S;Dawson, E;Forbes, S;Clements, J;Pettett, R;Dogan, A;Flanagan, A;Teague, J;Futreal, PA;Stratton, MR;Wooster, R
通讯作者：
Wooster, R
影响因子：
6.5
作者：
Au, Gough G.;Lincz, Lisa F.;Shafren, Darren R.
通讯作者：
Shafren, Darren R.
影响因子：
11.2
作者：
Diaconu, Iulia;Cerullo, Vincenzo;Hemminki, Akseli
通讯作者：
Hemminki, Akseli
DOI：
10.1073/pnas.96.15.8633
发表时间：
1999-07-20
影响因子：
11.1
作者：
Mumberg, D;Monach, PA;Schreiber, H
通讯作者：
Schreiber, H
影响因子：
6.4
作者：
Koks, Carolien A.;Garg, Abhishek D.;Van Gool, Stefaan W.
通讯作者：
Van Gool, Stefaan W.