title: The use of a tropism-modified measles virus in folate receptor-targeted virotherapy of ovarian cancer.
abstract: OBJECTIVE
  Attenuated measles viruses are promising experimental anticancer agents currently being evaluated in a phase I dose escalation trial for ovarian cancer patients. Virus attachment, entry, and subsequent intercellular fusion between infected and uninfected neighboring cells are mediated via the two measles receptors (CD46 and SLAM). To minimize potential toxicity due to measles virus-associated immunosuppression and infection of nontarget tissues, we sought to develop an ovarian cancer exclusive fully retargeted measles virus.
  
  
  RESULTS
  Interactions of measles virus with its natural receptors were ablated, and a single-chain antibody (scFv) specific for alpha-folate receptor (FRalpha), a target overexpressed on 90% of nonmucinous ovarian cancer, was genetically engineered on the viral attachment protein (MV-alphaFR). Specificity of virus tropism was tested on tumor and normal cells. Biodistribution of measles virus infection was evaluated in measles-susceptible CD46 transgenic mice, whereas antitumor activity was monitored noninvasively by bioluminescence imaging in xenograft models. Tropism and fusogenic activity of MV-alphaFR was redirected exclusively to FRalpha without compromise to virus infectivity. In contrast to the parental virus, MV-alphaFR has no background infectivity on normal human cells. The antitumor activity of MV-alphaFR, as assessed by tumor volume reduction and overall survival increase, was equal to the parental virus in two models of human ovarian cancer (s.c. and i.p.).
  
  
  CONCLUSIONS
  A FR-exclusive ovarian cancer targeted oncolytic virus was generated and shown to be therapeutically effective, thus introducing a new modality for FR targeting and a candidate measles virus for clinical testing.
authors.affiliation: Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
authors.forename: Kosei
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Takafumi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Mary
authors.initials: M
authors.lastname: Harvey
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Ann
authors.initials: A
authors.lastname: Oberg
authors.forename: Mariangela
authors.initials: M
authors.lastname: Figini
authors.forename: Silvana
authors.initials: S
authors.lastname: Canevari
authors.forename: Lynn C
authors.initials: LC
authors.lastname: Hartmann
authors.forename: Kah-Whye
authors.initials: KW
authors.lastname: Peng
mesh_terms: D019496:Cancer Vaccines; D002352:Carrier Proteins / Q000502:physiology*; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008214:Lymphocytes / Q000276:immunology*; D008459:Measles virus; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000821:virology; D011956:Receptors, Cell Surface / Q000502:physiology*; D012016:Reference Values; D014613:Vaccines, Attenuated; D014765:Viral Vaccines
chemical_list: D019496:Cancer Vaccines; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D014613:Vaccines, Attenuated; D014765:Viral Vaccines