title: Tumor cell-selective apoptosis induction through targeting of K(V)10.1 via bifunctional TRAIL antibody.
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-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.
authors: Max-Planck-Institut für Experimentelle Medizin, Hermann-Rein-Str, 3, 37075 Göttingen, Germany.
authors: Franziska
authors: F
authors: Hartung
authors: Walter
authors: W
authors: Stühmer
authors: Luis A
authors: LA
authors: Pardo
mesh_terms: D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D024201:Bystander Effect; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology*; D057127:Single-Chain Antibodies / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D051638:Ether-A-Go-Go Potassium Channels; C496884:KCNH1 protein, human; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D003513:Cycloheximide