Species D Adenoviruses as Oncolytic Viral Vectors.
Species D Adenoviruses as Oncolytic Viral Vectors.
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DOI：
10.3390/v12121399
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发表时间：
2020-12-06
期刊：
影响因子：
--
通讯作者：
Weaver EA
中科院分区：
文献类型：
--
作者：
Bullard BL;Corder BN;Weaver EA
溶瘤腺病毒（Ad）在肿瘤的治疗中显示出有希望的结果。5型广告（Ad 5）是最常用的广告类型。然而，使用Ad5作为溶瘤病毒存在几个限制，包括群体中高水平的抗Ad5中和抗体，Ad5六邻体与凝血因子X的结合导致肝脏隔离和毒性，以及许多肿瘤上初级受体CAR的表达降低。在这里，我们使用体外方法来探索四种不同的广告类型（广告26，28，45和48）属于物种D广告亚组和开发的复制能力物种D广告表达的人钠碘同向转运蛋白（hNIS）的组合放射病毒治疗的溶瘤潜力。我们评估了种D Ad载体在六种不同癌细胞系中的转导、复制、细胞毒性和基因表达。种属D Ads在SKBR 3乳腺癌细胞中显示出最大的转导和细胞毒性杀伤，其次是293、A549和HepG2细胞，但细胞毒性低于野生型Ad5病毒。相比之下，物种D的广告显示有限的转导和细胞毒性的Hela和SKOV3癌细胞系。这些D种Ad载体还在感染期间成功表达hNIS基因，导致多种癌细胞系中碘摄入增加。这些结果，抗物种D抗体的低血清阳性率，以及缺乏与凝血FX的结合，支持进一步探索物种D广告作为针对多种类型癌症的替代溶瘤腺病毒。
Oncolytic adenoviruses (Ad) have shown promising results in the therapeutic treatment of cancer. Ad type 5 (Ad5) is the most extensively utilized Ad type. However, several limitations exist to using Ad5 as an oncolytic virus, including high levels of anti-Ad5 neutralizing antibodies in the population, binding of the Ad5 hexon to blood coagulation factor X leading to liver sequestration and toxicity, and reduced expression of the primary receptor CAR on many tumors. Here, we use in vitro methods to explore the oncolytic potential of four alternative Ad types (Ad26, 28, 45, and 48) belonging to the species D Ad subgroup and developed replication-competent species D Ads expressing the human sodium iodide symporter protein (hNIS) for combination radiovirotherapy. We evaluated the species D Ad vectors transduction, replication, cytotoxicity, and gene expression in six different cancer cell lines. Species D Ads showed the greatest transduction and cytotoxic killing in the SKBR3 breast cancer cells, followed by 293, A549, and HepG2 cells, however the cytotoxicity was less than the wild type Ad5 virus. In contrast, species D Ads showed limited transduction and cytotoxicity in the Hela and SKOV3 cancer cell lines. These species D Ad vectors also successfully expressed the hNIS gene during infection leading to increased iodide uptake in multiple cancer cell lines. These results, the low seroprevalence of anti-species D antibodies, and the lack of binding to blood coagulation FX, support further exploration of species D Ads as alternative oncolytic adenoviruses against multiple types of cancer.
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影响因子：
5.4
作者：
Dhar, Debanjan;Spencer, Jacqueline F.;Wold, William S. M.
通讯作者：
Wold, William S. M.
影响因子：
5.4
作者：
Chen, H.;Xiang, Z. Q.;Ertl, H. C. J.
通讯作者：
Ertl, H. C. J.
影响因子：
5.8
作者：
Hedley, Susan J.;Chen, Jian;Kovesdi, Imre
通讯作者：
Kovesdi, Imre
DOI：
10.1128/cdli.11.2.351-357.2004
发表时间：
2004-03-01
期刊：
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY
影响因子：
--
作者：
Nwanegbo, E;Vardas, E;Gambotto, A
通讯作者：
Gambotto, A
影响因子：
6.7
作者：
Stichling N;Suomalainen M;Flatt JW;Schmid M;Pacesa M;Hemmi S;Jungraithmayr W;Maler MD;Freudenberg MA;Plückthun A;May T;Köster M;Fejer G;Greber UF
通讯作者：
Greber UF