title: Systemically delivered measles virus-infected mesenchymal stem cells can evade host immunity to inhibit liver cancer growth.
abstract: OBJECTIVE
  Although attenuated measles virus (MV) has demonstrated potent oncolytic activities towards human cancers, it has not yet been widely adopted into clinical practice. One of the major hurdles is the presence of pre-existing anti-MV immunity in the recipients. In this study, we have evaluated the combination of the potent oncolytic activity of the attenuated MV with the unique immunoprivileged and tumor-tropic biological properties of human bone marrow-derived mesenchymal stem cells (BM-hMSCs) to combat human hepatocellular carcinoma (HCC), orthotopically implanted in SCID mice, passively immunized with human neutralizing antibodies against MV as a preclinical model.
  
  
  METHODS
  SCID mice were orthotopically implanted with patient-derived HCC tissues and established HCC cell lines. SCID mice were passively immunized with human neutralizing anti-measles antibodies. Bioluminescence and fluorescence imaging were employed to monitor the ability of systemically delivered MV-infected BM-hMSCs to infiltrate the implanted tumors and their effects on tumor growth.
  
  
  RESULTS
  Systemically delivered MV-infected BM-hMSCs homed to the HCC tumors implanted orthotopically in the liver and it was evidenced that BM-hMSCs could transfer MV infectivity to HCC via heterofusion. Furthermore, therapy with MV-infected BM-hMSCs resulted in significant inhibition of tumor growth in both measles antibody-naïve and passively-immunized SCID mice. By contrast, when cell-free MV viruses were delivered systemically, antitumor activity was evident only in measles antibody-naïve SCID mice.
  
  
  CONCLUSIONS
  MV-infected BM-hMSCs cell delivery system provides a feasible strategy to elude the presence of immunity against MV in most of the potential cancer patients to be treated with the oncolytic MV viruses.
authors.affiliation: Bek Chai Heah Laboratory of Cancer Genomics, Humphrey Oei Institute of Cancer Research, Singapore.
authors.forename: Hooi-Tin
authors.initials: HT
authors.lastname: Ong
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Federspiel
authors.forename: Chang M
authors.initials: CM
authors.lastname: Guo
authors.forename: London Lucien
authors.initials: LL
authors.lastname: Ooi
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Russell
authors.forename: Kah-Whye
authors.initials: KW
authors.lastname: Peng
authors.forename: Kam M
authors.initials: KM
authors.lastname: Hui
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000276:immunology / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000473:pathology / Q000821:virology; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000517:prevention & control / Q000821:virology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D004195:Disease Models, Animal; D064593:Heterografts; D006801:Humans; D007116:Immunization, Passive / Q000379:methods; D008113:Liver Neoplasms / Q000473:pathology* / Q000517:prevention & control* / Q000821:virology; D008459:Measles virus / Q000276:immunology / Q000472:pathogenicity*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000473:pathology / Q000821:virology*; D051379:Mice; D016513:Mice, SCID; D050504:Oncolytic Viruses / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral
keywords: Hepatocellular carcinoma; Human neutralizing antibody; Mesenchymal stem cells as cell delivery vehicles; Oncolytic measles virus; Orthotopically implanted HCC tumor model; Systemic virotherapy