A bispecific EpCAM/CD133-targeted toxin is effective against carcinoma.
A bispecific EpCAM/CD133-targeted toxin is effective against carcinoma.
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DOI：
10.1007/s11523-013-0290-9
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发表时间：
2014-09
影响因子：
5.4
通讯作者：
Vallera DA
中科院分区：
文献类型：
--
作者：
Waldron NN;Barsky SH;Dougherty PR;Vallera DA
The discovery of chemoresistant cancer stem cells (CSCs) in carcinomas has created the need for therapies that specifically target these subpopulations of cells. Here we characterized a bispecific targeted toxin that is composed of two antibody fragments and a catalytic protein toxin allowing it to bind two CSC markers on the same cell and kill this resistant subpopulation. CD133 is a well-known CSC marker and has been successfully targeted and caused regression of head and neck squamous cell carcinoma (HNSCC) in vivo. To enable it to bind a broader range of CSCs, an anti-EpCAM scFv was added to create dEpCAMCD133KDEL, a deimmunized bispecific targeted toxin on a single amino acid chain. This bispecific potently inhibited protein translation and proliferation in vitro in three different types of carcinoma. Furthermore, in a CSC spheroid model dEpCAMCD133KDEL eliminated Mary-X spheroids, an inflammatory breast carcinoma. Finally, this bispecific also caused tumor regression in an in vivo model of HNSCC. This represents the first bispecific CSC targeted toxin and warrants further development as a possible therapy for carcinoma.
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DOI：
10.1073/pnas.0804851105
发表时间：
2008-08-12
影响因子：
11.1
作者：
Onda, Masanori;Beers, Richard;Pastan, Ira
通讯作者：
Pastan, Ira
影响因子：
4.7
作者：
Skubitz AP;Taras EP;Boylan KL;Waldron NN;Oh S;Panoskaltsis-Mortari A;Vallera DA
通讯作者：
Vallera DA
影响因子：
10.8
作者：
Suuronen, EJ;Wong, S;Ruel, M
通讯作者：
Ruel, M
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
11.2
作者：
Dallas NA;Xia L;Fan F;Gray MJ;Gaur P;van Buren G 2nd;Samuel S;Kim MP;Lim SJ;Ellis LM
通讯作者：
Ellis LM