Abstract
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 killing 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-epithelial cell adhesion molecule (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.
Original language | English (US) |
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Pages (from-to) | 239-249 |
Number of pages | 11 |
Journal | Targeted Oncology |
Volume | 9 |
Issue number | 3 |
DOIs | |
State | Published - Sep 2014 |
Bibliographical note
Publisher Copyright:© 2013, Springer-Verlag France.
Keywords
- CD133
- Cancer stem cells
- EpCAM
- Head and neck squamous cell carcinoma
- Immunotoxins
- Targeted toxins