title: Specific elimination of CD133+ tumor cells with targeted oncolytic measles virus.
abstract: Tumor-initiating cells (TIC) are critical yet evasive targets for the development of more effective antitumoral strategies. The cell surface marker CD133 is frequently used to identify TICs of various tumor entities, including hepatocellular cancer and glioblastoma. Here, we describe oncolytic measles viruses (MV) retargeted to CD133. The viruses, termed MV-141.7 and MV-AC133, infected and selectively lysed CD133(+) tumor cells. Both viruses exerted strong antitumoral effects on human hepatocellular carcinoma growing subcutaneously or multifocally in the peritoneal cavity of nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Notably, the CD133-targeted viruses were more effective in prolonging survival than the parental MV-NSe, which is currently assessed as oncolytic agent in clinical trials. Interestingly, target receptor overexpression or increased spreading kinetics through tumor cells were excluded as being causative for the enhanced oncolytic activity of CD133-targeted viruses. MV-141.7 was also effective in mouse models of orthotopic glioma tumor spheres and primary colon cancer. Our results indicate that CD133-targeted measles viruses selectively eliminate CD133(+) cells from tumor tissue, offering a key tool for research in tumor biology and cancer therapy.
authors.affiliation: Medical Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, Langen, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Bach
authors.forename: Tobias
authors.initials: T
authors.lastname: Abel
authors.forename: Christopher
authors.initials: C
authors.lastname: Hoffmann
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Gal
authors.forename: Gundula
authors.initials: G
authors.lastname: Braun
authors.forename: Iris
authors.initials: I
authors.lastname: Voelker
authors.forename: Claudia R
authors.initials: CR
authors.lastname: Ball
authors.forename: Ian C D
authors.initials: IC
authors.lastname: Johnston
authors.forename: Ulrich M
authors.initials: UM
authors.lastname: Lauer
authors.forename: Christel
authors.initials: C
authors.lastname: Herold-Mende
authors.forename: Michael D
authors.initials: MD
authors.lastname: Mühlebach
authors.forename: Hanno
authors.initials: H
authors.lastname: Glimm
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Buchholz
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000628:therapy; D005910:Glioma / Q000628:therapy; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000628:therapy*; D008459:Measles virus; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D058990:Molecular Targeted Therapy; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000821:virology; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses; D010455:Peptides / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse