title: Bioinformatic prediction and experimental validation of a PE38-based recombinant immunotoxin targeting the Fn14 receptor in cancer cells.
abstract: OBJECTIVE
  AFn14R can serve as an ideal target for cancer immunotherapy. Here, a combined bioinformatic and experimental approach was applied to characterize an immunotoxin consisting of single-chain variable fragment antibody that targets Fn14 and a toxin fragment (PE38).
  
  
  RESULTS
  Flow cytometry results showed that the rate of PE38-P4A8 binding to Fn14 was approximately 60 and 40% in HT-29 and A549 cells, respectively. Moreover, 1 ng/µl of immunotoxin was able to lyse approximately 53 and 41% of HT-29 and A549, respectively. PE38-P4A8 showed stability in mouse serum (∼90%) after 3-h incubation. Most importantly, using bioinformatics for determining the structure and function of fusion proteins can be very helpful in designing of experiments.
  
  
  CONCLUSIONS
  Coupled with bioinformatics, experimental approaches revealed that PE38-P4A8 could be used as a promising therapeutic agent for cancer cells expressing Fn14.
authors.affiliation: Division of Microbiology, Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Keshtvarz
authors.affiliation: Chemical Injuries Research Center, Baqiyatallah, University of Medical Sciences, Tehran, Iran.
authors.forename: Jafar
authors.initials: J
authors.lastname: Salimian
authors.affiliation: Department of Epidemiology & Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Yaseri
authors.affiliation: Department of Clinical Biochemistry, Tarbiat Modares University, Tehran, Iran.
authors.forename: Seyedeh Zahra
authors.initials: SZ
authors.lastname: Bathaie
authors.affiliation: Applied Microbiology Research Center, Baqiyatallah University of Medical Sciences, Vanak Sq. Molasadra St, Tehran, Iran.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Rezaie
authors.affiliation: Division of Microbiology, Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Aliramezani
authors.affiliation: Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Norouzbabaei
authors.affiliation: Applied Microbiology Research Center, Baqiyatallah University of Medical Sciences, Vanak Sq. Molasadra St, Tehran, Iran.
authors.forename: Jafar
authors.initials: J
authors.lastname: Amani
authors.affiliation: Division of Microbiology, Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.|Food Microbiology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Douraghi
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000628:therapy*; D000951:Antigens, Neoplasm / Q000378:metabolism*; D019295:Computational Biology; D006801:Humans; D000922:Immunotoxins / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D057127:Single-Chain Antibodies / Q000235:genetics / Q000378:metabolism*; D000074050:TWEAK Receptor
chemical_list: D000951:Antigens, Neoplasm; D000922:Immunotoxins; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies; C000613297:TNFRSF12A protein, human; D000074050:TWEAK Receptor; C000613299:Tnfrsf12a protein, mouse
keywords: Fn14R; cancer; immunogenicitiy; immunotoxin