title: Antitumoral activity of parvovirus-mediated IL-2 and MCP-3/CCL7 delivery into human pancreatic cancer: implication of leucocyte recruitment.
abstract: Pancreatic ductal adenocarcinoma (PDAC) represents the fourth leading cause of cancer-related death in western countries. The patients are often diagnosed in advanced metastatic stages, and the prognosis remains extremely poor with an overall 5-year survival rate less than 5 %. Currently, novel therapeutic strategies are being pursued to combat PDAC, including oncolytic viruses, either in their natural forms or armed with immunostimulatory molecules. Natural killer cells are critical players against tumours and infected cells. Recently, we showed that IL-2-activated human NK cells displayed killing activity against PDAC cells, which could further be enhanced through the infection of PDAC cells with the rodent parvovirus H-1PV. In this study, the therapeutic efficacy of parvovirus-mediated delivery of three distinct cyto/chemokines (Il-2, MCP-3/CCL7 and IP-10/CXCL10) was evaluated in xenograft models of human PDAC. We show here that activated NK and monocytic cells were found to be recruited by PDAC tumours upon infection with parvoviruses armed with IL-2 or the chemokine MCP-3/CCL7, resulting in a strong anti-tumour response.
authors.affiliation: Laboratory of Molecular Immunology, Rega Institute for Medical Research, K.U. Leuven, Leuven, Belgium.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dempe
authors.forename: Muriel
authors.initials: M
authors.lastname: Lavie
authors.forename: Sofie
authors.initials: S
authors.lastname: Struyf
authors.forename: Rauf
authors.initials: R
authors.lastname: Bhat
authors.forename: Hannelien
authors.initials: H
authors.lastname: Verbeke
authors.forename: Stephanie
authors.initials: S
authors.lastname: Paschek
authors.forename: Nele
authors.initials: N
authors.lastname: Berghmans
authors.forename: Renate
authors.initials: R
authors.lastname: Geibig
authors.forename: Jean
authors.initials: J
authors.lastname: Rommelaere
authors.forename: Jo
authors.initials: J
authors.lastname: Van Damme
authors.forename: Christiane
authors.initials: C
authors.lastname: Dinsart
mesh_terms: D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology / Q000628:therapy*; D045744:Cell Line, Tumor; D054410:Chemokine CCL7 / Q000235:genetics / Q000276:immunology*; D054357:Chemokine CXCL10 / Q000276:immunology; D005260:Female; D052661:H-1 parvovirus; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D007962:Leukocytes / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D009000:Monocytes / Q000276:immunology; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000628:therapy*; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: C515450:CCL7 protein, human; C114753:CXCL10 protein, human; D054410:Chemokine CCL7; D054357:Chemokine CXCL10; C508594:IL2 protein, human; D007376:Interleukin-2