Therapeutic improvement of a stroma-targeted CRAd by incorporating motives responsive to the melanoma microenvironment.
Therapeutic improvement of a stroma-targeted CRAd by incorporating motives responsive to the melanoma microenvironment.
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DOI：
10.1038/jid.2013.191
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发表时间：
2013-11
影响因子：
6.5
通讯作者：
Lopez, M. Veronica
中科院分区：
文献类型：
--
作者：
Viale, Diego L.;Cafferata, Eduardo G.;Gould, David;Rotondaro, Cecilia;Chernajovsky, Yuti;Curiel, David T.;Podhajcer, Osvaldo L.;Lopez, M. Veronica
We have previously designed a conditionally replicative oncolytic adenovirus (CRAd) named Ad-F512 that can target both the stromal and the malignant melanoma cell compartments. The replication capacity of this CRAd is driven by a 0.5-Kb SPARC promoter fragment (named F512). To improve CRAd’s efficacy, we cloned into F512 motives responsive to hypoxia (hypoxia-responsive element (HRE)) and inflammation (nuclear factor kappa B) to obtain a chimeric promoter named κBF512HRE. Using luciferase as a reporter gene, we observed 10–15-fold increased activity under hypoxia and 10–80-fold induction upon tumor necrosis factor-α addition. We next constructed a CRAd (Ad-κBF512HRE) where E1A activity was under κBF512HRE regulation. Treatment of nude mice harboring established tumors made of a mix of SB2 melanoma cells and WI-38 fibroblasts with Ad-κBF512HRE led to the complete elimination of tumors in 100% of mice (8/8). Moreover, Ad-5/3-κBF512HRE, a viral variant pseudotyped with a chimeric 5/3 fiber, exerted a strong lytic effect on CAR-negative melanoma cells and was highly effective in vivo on established tumors made of melanoma cells and WI-38 fibroblasts, leading to the complete elimination of 4/5 tumors. These results indicate that this improved stroma-targeted oncolytic adenovirus can override the resistance of melanoma tumors and might become of significant importance for melanoma therapeutics.
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影响因子：
2.7
作者：
Juven-Gershon, Tamar;Kadonaga, James T.
通讯作者：
Kadonaga, James T.
DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
5.1
作者：
Modlich, U;Pugh, CW;Bicknell, R
通讯作者：
Bicknell, R
影响因子：
3.5
作者：
Khoury, M.;Adriaansen, J.;Apparailly, F.
通讯作者：
Apparailly, F.
影响因子：
5.1
作者：
Lee, JY;Lee, YS;Kim, DK
通讯作者：
Kim, DK