A bispecific EpCAM/CD133-targeted toxin is effective against carcinoma
| Autor: | Sanford H. Barsky, Nate N. Waldron, Daniel A. Vallera, Phillip Dougherty |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
Mice Nude Biology Transfection Article Mice chemistry.chemical_compound Antigens CD Antigens Neoplasm Cancer stem cell Immunotoxin In vivo Antibodies Bispecific medicine Animals Humans Pharmacology (medical) AC133 Antigen Cell Proliferation Glycoproteins Squamous Cell Carcinoma of Head and Neck Cell adhesion molecule Immunotoxins Epithelial cell adhesion molecule Epithelial Cell Adhesion Molecule medicine.disease Head and neck squamous-cell carcinoma Molecular biology Cell killing Oncology chemistry Head and Neck Neoplasms Carcinoma Squamous Cell Neoplastic Stem Cells Caco-2 Cells Peptides Cell Adhesion Molecules |
| Zdroj: | Targeted Oncology. 9:239-249 |
| ISSN: | 1776-260X 1776-2596 |
| DOI: | 10.1007/s11523-013-0290-9 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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