与野生型HSV-1相比,HF10毒力更低并且复制能力更前,其安全性和有效性在许多动物模型中得以证实,已被用于治疗卵巢癌、恶性黑素瘤、乳腺癌和胰腺癌的临床试验。 BS001 是第一种用于临床的oHSV-2。通过删除ICP34.5促进病毒在肿瘤细胞中选择性复制,增强安全性; 删除毒力基因ICP47,降低免疫抑制,促进病毒复制,增强抗...
例如,对常用oHSV-1病毒的ICP34.5(RL1)、ICP47、US11、TK等特定基因进行敲除,使其具有肿瘤选择性。另一方面,在特定位点插入外源基因,如粒细胞-巨噬细胞集落刺激因子(GM-CSF)、IL12等增强免疫反应。为了进一步提高其肿瘤靶向性和安全性,可根据需求对HSV-1进行改造。拥有HSV-1毒株种类有KOS株、F株、H129株。
Bilateral tumor models were used and only one tumor was treated via intratumoral injection with HSV-1/ICP34.5-/ICP47-/mFLT3L/mIL12. Anti-tumor responses were evaluated in the injected tumor (local response), the uninjected tumor (abscopal) and via splenic immune profiling (systemic). HSV-1...
ICP34.5- and ICP47-deficient HSV-1 (HSV-1 Δ34.5/Δ47; referred to as oHSV from here onwards) was created by deleting the coding sequences of ICP34.5 and ICP47 in a bacterial artificial chromosome (BAC) using a two-step Red-mediated recombination method55. Quantitative real-time polymeras...
Krystal Biotech 将 HSV-1 固有的许多有益特性与 ICP4 和ICP22 中靶向 IE 基因缺失的修饰策略相结合,使载体无法复制且细胞毒性较低,从而开发出一种体内、非侵入性和适用于局部基因递送的可重复给药载体平台(图1)。此外,Krystal Biotech ...
ICP47可抑制MHC-1递呈抗原,如G47Δ,其能激活机体免疫系统对肿瘤的清除。 TK是由UL23基因编码的胸苷激酶(Thymidine kinase,TK)。dlspTk是早期的一株缺 失TK基因的重组HSV-1,其在正常细胞中的复制能力减弱, 但可借助肿瘤细胞富含的TK而特异性地在肿瘤细胞中复制。TK是 脱氧核糖核苷三磷酸(Deoxyribonucleoside triph...
GreenYellow #adff2f 173,255,47 0.2324,0.8157,1.0000 0.3216,0.0000,0.8157,0.0000 honeydew1 #f0fff0 240,255,240 0.3333,0.0588,1.0000 0.0588,0.0000,0.0588,0.0000 honeydew2 #e0eee0 224,238,224 0.3333,0.0588,0.9333 0.0588,0.0000,0.0588,0.0667 honeydew3 #c1cdc1 193,205,193 0.3333,0.0585,0.8039 ...
ICP47可抑制MHC7递呈抗原,如G474,其能激活机体免疫系统对肿瘤的清除。TK是由UL23基因编码的胸背激酶(Thymidinekinase,TK)。dlspTk是早期的一株缺失TK基因的重组HSV-1,其在正常细胞中的复制能力减弱,但可借助肿瘤细胞富含的TK而特异性地在肿瘤细胞中复制。TK是脱氧核糖核甘三磷酸(Deoxyribonucleosidetriphosphate,dNTP...
根据本发明实施例的HSV病毒载体可以持续高表达趋化因子CCL19,有效抑制肿瘤。 专利权项:1.一种HSV病毒载体,其特征在于,所述HSV病毒载体的ICP47、ICP34.5基因沉默,以及携带CCL19基因。 百度查询: 广东东阳光药业有限公司 HSV病毒载体及其应用专利 免责声明 1、本报告根据公开、合法渠道获得相关数据和信息,力求客观、...
1 for 12 h were analyzed by RT-qPCR for IDO1 mRNA level (n = 3; Data were shown as means ± SEM).f,gHepa1-6 cells were treated with 5 MOI HSV-1 or 5 MOI HSV-1 plus 1 μM Navoximod (V-Navo).fRT-qPCR analysis of gD (left) and ICP47 (right) DNA level ...