Tumor cell-selective apoptosis induction through targeting of K_V10.1 via bifunctional TRAIL antibody

• Main Authors: Pardo Luis A, Stühmer Walter, Hartung Franziska
• Format: Article
• Language: English
• Published: BMC 2011-09-01
• Series: Molecular Cancer
• Subjects: K_V10.1; Eag1; scFv62-TRAIL
• Online Access: http://www.molecular-cancer.com/content/10/1/109

<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_V10.1 (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_V10.1 (scFv62) and fused it to the human soluble TRAIL. The K_V10.1-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_V10.1 were treated with the purified construct. After sensitization with cytotoxic drugs, scFv62-TRAIL induced apoptosis only in K_V10.1-positive cancer cells, but not in non-tumor cells, nor in tumor cells lacking K_V10.1 expression. In co-cultures with K_V10.1-positive cancer cells the fusion protein also induced apoptosis in bystander K_V10.1-negative cancer cells, while normal prostate epithelial cells were not affected when present as bystander.</p> <p>Conclusions</p> <p>K_V10.1 represents a novel therapeutic target for cancer. We could design a strategy that selectively kills tumor cells based on a K_V10.1-specific antibody.</p>