TY - JOUR T1 - Antitumoral activity of parvovirus-mediated IL-2 and MCP-3/CCL7 delivery into human pancreatic cancer: implication of leucocyte recruitment JF - Cancer Immunol Immunother Y1 - 2012 A1 - S. Dempe A1 - M. Lavie A1 - S. Struyf A1 - R. Bhat A1 - H. Verbeke A1 - S. Paschek A1 - N. Berghmans A1 - R. Geibig A1 - J. Rommelaere A1 - J. Van Damme A1 - C. Dinsart KW - chemokine KW - IL-2 KW - Pancreatic carcinoma KW - Parvovirus AB -

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.

VL - 61 CP - 11 M3 - 10.1007/s00262-012-1279-4 ER -