title: Inactivated orf virus (Parapoxvirus ovis) induces antitumoral activity in transplantable tumor models.
abstract: Orf virus (ORFV, Parapoxvirus ovis) possesses strong immunomodulating activity including the induction of interferon gamma (IFN-γ) and interleukin-12 (IL-12) expression. Antiviral effects have been described which appeared to be facilitated by an ORFV-induced Type 1 helper T-cell (Th1-type) immune response. In this study, we investigated the potential antitumoral activity of inactivated ORFV in transplantable tumor models. We show that parenteral administration of inactivated ORFV mediates antitumor effects in various models including the murine syngenic B16 F10 melanoma and MDA-MB-231 human breast cancer xenograft. Inhibition of natural killer (NK) and NKT cell activity through administration of an anti-mouse NK-1.1 antibody led to a reduction of ORFV-mediated antitumoral effects. However, residual antitumoral activity was observed. This observation was confirmed in MDA-MB-231 tumor-bearing NOD/LtSz-scid/j mice which not only lack functional T and B lymphocytes but, in addition, have virtually no cells positive for the NK 1.1 cell surface marker. Thus, administration of inactivated ORFV induced inhibitory effects on the growth of transplantable tumors even under conditions of severe immunosuppression.
authors.affiliation: Tumor Biology Center, the University of Freiburg, Freiburg, Germany.
authors.forename: Heinz-Herbert
authors.initials: HH
authors.lastname: Fiebig
authors.forename: Angela
authors.initials: A
authors.lastname: Siegling
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Astrid
authors.initials: A
authors.lastname: Friebe
authors.forename: Percy
authors.initials: P
authors.lastname: Knolle
authors.forename: Andreas
authors.initials: A
authors.lastname: Limmer
authors.forename: Olaf
authors.initials: O
authors.lastname: Weber
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000276:immunology; D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007107:Immune System; D007167:Immunotherapy / Q000379:methods; D018664:Interleukin-12 / Q000378:metabolism; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009923:Orf virus / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D018664:Interleukin-12