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Antitumoral activity of parvovirus-mediated IL-2 and MCP-3/CCL7 delivery into human pancreatic cancer: implication of leucocyte recruitment

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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.

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Acknowledgments

We are grateful to Ghislain Opdenakker for kindly providing human MCP-3 cDNA, Nathalie Salomé and Juerg Nuesch for helpful discussions, Chris Dillen, Alexandra Stroh-Dege and Claudia Plotsky for technical assistance. Laura Whiele is acknowledged for her help in the production of viral stocks. This work was supported by the Fund for Scientific Research of Flanders (F.W.O.-Vlaanderen, contract number G064809, J.V.D.), the Interuniversity Attraction Poles (I.A.P.) Program-Belgian Science Policy (J.V.D.) and the European Union 6FP EC contract INNOCHEM (J.V.D.).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Laboratory of Molecular Immunology, Rega Institute for Medical Research, K.U. Leuven, Leuven, Belgium

    Sebastian Dempe, Sofie Struyf, Hannelien Verbeke, Nele Berghmans & Jo Van Damme

  2. Tumor Virology Division, Abt F010, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120, Heidelberg, Germany

    Sebastian Dempe, Muriel Lavie, Sofie Struyf, Rauf Bhat, Stephanie Paschek, Renate Geibig, Jean Rommelaere & Christiane Dinsart

  3. INSERM U701, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120, Heidelberg, Germany

    Muriel Lavie, Stephanie Paschek, Jean Rommelaere & Christiane Dinsart

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  1. Sebastian Dempe
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Dempe, S., Lavie, M., Struyf, S. et al. Antitumoral activity of parvovirus-mediated IL-2 and MCP-3/CCL7 delivery into human pancreatic cancer: implication of leucocyte recruitment. Cancer Immunol Immunother 61, 2113–2123 (2012). https://doi.org/10.1007/s00262-012-1279-4

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