**2. Parvovirus-Based Combinatorial Immunotherapy against Pancreatic Cancer**

PDAC is the most common neoplasm of the pancreas and one of the most aggressive human cancers. It is characterized by quick progression, broad intraperitoneal dissemination (peritoneal carcinomatosis) and frequent resistance to conventional treatments. PDAC is usually diagnosed at advanced stages, when surgical resection is either not feasible or inefficient, as most patients eventually suffer from local recurrence and metachronous metastasis [20]. Current chemotherapy regimens achieve only minor improvements of PDAC dismal prognosis: the median survival time and overall 5-year survival remain as low as <12 months and approximately 5%, respectively [21]. Gemzar (gemcitabine) is the standard drug used to treat PDAC patients after surgery. Yet, gemcitabine only prolongs the survival of the majority (82%) of the patients by less than two-fold. On the same line, pathway-specific targeted therapies showed little efficacy against PDAC [22]. Therefore, new treatment paradigms need to be urgently explored in order to extend PDAC patient life expectancy and offer better quality of life.

H-1PV is among the oncolytic viruses (OVs), which have promising potential for efficiently targeting pancreatic cancer. PDAC sensitivity to H-1PV-induced oncolysis was demonstrated in various preclinical models [23,24]. Infection of human PDAC-derived cells leads to their killing, which is mediated at least in part by cathepsins [24]. Importantly, H-1PV sensitivity is preserved in gemcitabine-resistant cultures [23], thus opening up prospects to circumvent PDAC resistance to current standard death inducers.
