| Summary: | <p>Abstract</p> <p>Background</p> <p>The search for strategies to target ion channels for therapeutic applications has become of increasing interest. Especially, the potassium channel K<sub>V</sub>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.</p> <p>Methods</p> <p>We designed a single-chain antibody against an extracellular region of K<sub>V</sub>10.1 (scFv62) and fused it to the human soluble TRAIL. The K<sub>V</sub>10.1-specific scFv62 antibody -TRAIL fusion protein was expressed in CHO-K1 cells, purified by chromatography and tested for biological activity.</p> <p>Results</p> <p>Prostate cancer cells, either positive or negative for K<sub>V</sub>10.1 were treated with the purified construct. After sensitization with cytotoxic drugs, scFv62-TRAIL induced apoptosis only in K<sub>V</sub>10.1-positive cancer cells, but not in non-tumor cells, nor in tumor cells lacking K<sub>V</sub>10.1 expression. In co-cultures with K<sub>V</sub>10.1-positive cancer cells the fusion protein also induced apoptosis in bystander K<sub>V</sub>10.1-negative cancer cells, while normal prostate epithelial cells were not affected when present as bystander.</p> <p>Conclusions</p> <p>K<sub>V</sub>10.1 represents a novel therapeutic target for cancer. We could design a strategy that selectively kills tumor cells based on a K<sub>V</sub>10.1-specific antibody.</p>
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