title: Regression of glioma in rat models by intranasal application of parvovirus h-1.
abstract: OBJECTIVE
  In previous studies, we have shown that the apathogenic rat parvovirus H-1 (H-1PV) is capable to induce regression of advanced symptomatic rat and human gliomas in a rat model, when the virus was injected in the tumor (intracranially) or intravenously. Infection with H-1PV did not provoke any pathology in nontumor tissue. This study addresses the question whether also intranasal application of this oncolytic virus is suitable and sufficient for treating gliomas in this animal model.
  
  
  METHODS
  Rat (RG-2) or human (U87) glioma cells were grafted stereotactically in the brain of rats (Wistar or RNU, respectively), and after development of tumors visible by MRI, H-1PV was instilled intranasally. Tumor regression was monitored by MRI, and survival was analyzed by Kaplan-Meier analysis. Brains from sacrificed animals were analyzed for histologic alterations, presence of viral DNA and proteins and infectious virions. In addition, distribution of virus to other organs was determined.
  
  
  RESULTS
  A single intranasal instillation of H-1PV was sufficient to induce efficient regression of rat glioma, leading to significant prolongation of survival without any toxicity for other tissues. It is shown that the virus reaches brain and other tissues, and that the viral replication-associated (and oncolysis-associated) regulatory proteins are exclusively expressed in the tumor tissue. In rats with xenografts of human glioma, oncolytic activity of H-1PV was less pronounced, however, leading to significant prolongation of survival.
  
  
  CONCLUSIONS
  In view of an ongoing clinical trial on the use of H-1PV for oncolytic virotherapy of glioma, the option of applying the virus intranasally may be a valuable alternative to invasive routes of infection.
authors.affiliation: Division of Tumor Virology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Irina
authors.initials: I
authors.lastname: Kiprianova
authors.forename: Nadja
authors.initials: N
authors.lastname: Thomas
authors.forename: Ali
authors.initials: A
authors.lastname: Ayache
authors.forename: Manuel
authors.initials: M
authors.lastname: Fischer
authors.forename: Barbara
authors.initials: B
authors.lastname: Leuchs
authors.forename: Michèle
authors.initials: M
authors.lastname: Klein
authors.forename: Jean
authors.initials: J
authors.lastname: Rommelaere
authors.forename: Jörg R
authors.initials: JR
authors.lastname: Schlehofer
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000473:pathology / Q000821:virology; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D005910:Glioma / Q000473:pathology / Q000628:therapy* / Q000821:virology; D052661:H-1 parvovirus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D050130:Oncolytic Virotherapy / Q000379:methods*; D010322:Parvoviridae Infections / Q000473:pathology / Q000628:therapy* / Q000821:virology; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D047368:Tumor Burden; D014764:Viral Proteins / Q000032:analysis; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
chemical_list: D004279:DNA, Viral; D014764:Viral Proteins