Tumor cell-selective apoptosis induction through targeting of K(V)10.1 via 
bifunctional TRAIL antibody

Hartung, F.; Stuhmer, W.; Pardo, L. A.

doi:10.1186/1476-4598-10-109

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Journal Article

Tumor cell-selective apoptosis induction through targeting of K(V)10.1 via bifunctional TRAIL antibody

MPS-Authors

Hartung, F.
Max Planck Society;

Stuhmer, W.
Max Planck Society;

Pardo, L. A.
Max Planck Society;

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https://www.ncbi.nlm.nih.gov/pubmed/21899742
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Citation

Hartung, F., Stuhmer, W., & Pardo, L. A. (2011). Tumor cell-selective apoptosis induction through targeting of K(V)10.1 via bifunctional TRAIL antibody. Mol Cancer, 10, 109. doi:10.1186/1476-4598-10-109.

Cite as: https://hdl.handle.net/21.11116/0000-0009-F233-C

Abstract

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-a-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.