Tumor cell-selective apoptosis induction through targeting of K(V)10.1 via bifunctional TRAIL antibody.
Mol Cancer
; 10: 109, 2011 Sep 07.
Article
em En
| MEDLINE
| ID: mdl-21899742
BACKGROUND: The search for strategies to target ion channels for therapeutic applications has become of increasing interest. Especially, the potassium channel K(V)10.1 (Ether-á-go-go) is attractive as target since this surface protein is virtually not detected in normal tissue outside the central nervous system, but is expressed in approximately 70% of tumors from different origins. METHODS: We designed a single-chain antibody against an extracellular region of K(V)10.1 (scFv62) and fused it to the human soluble TRAIL. The K(V)10.1-specific scFv62 antibody -TRAIL fusion protein was expressed in CHO-K1 cells, purified by chromatography and tested for biological activity. RESULTS: Prostate cancer cells, either positive or negative for K(V)10.1 were treated with the purified construct. After sensitization with cytotoxic drugs, scFv62-TRAIL induced apoptosis only in K(V)10.1-positive cancer cells, but not in non-tumor cells, nor in tumor cells lacking K(V)10.1 expression. In co-cultures with K(V)10.1-positive cancer cells the fusion protein also induced apoptosis in bystander K(V)10.1-negative cancer cells, while normal prostate epithelial cells were not affected when present as bystander. CONCLUSIONS: K(V)10.1 represents a novel therapeutic target for cancer. We could design a strategy that selectively kills tumor cells based on a K(V)10.1-specific antibody.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Recombinantes de Fusão
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Biomarcadores Tumorais
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Apoptose
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Canais de Potássio Éter-A-Go-Go
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Ligante Indutor de Apoptose Relacionado a TNF
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Anticorpos de Cadeia Única
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Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Mol Cancer
Ano de publicação:
2011
Tipo de documento:
Article