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For quite a long time oncolytic viruses (OVs) have been regarded merely as specific tumor cell killers, while disregarding the fact that all oncolytic activities take place in the context of a functional immune system. Oncolytic parvoviruses (PV) represent non-pathogenic, naturally oncolytic (non-modified), animal (rodent) viruses with a tropism that extends to a number of transformed human cells. Our recent work using various animal models substantiates the contention that H-1PV acts as both an oncolytic agent and an adjuvant, by direct cytoreduction in the tumor and bystander antitumor immunity. ImmunostimulatoryCpG motifs were incorporated into the singlestranded DNA genome of H-1PV and our current objective was to test whether the CpG-armed virus was in possession of an enhanced adjuvant capacity. The immunogenic potential of the CpG-enriched parvoviral derivative (JabCG) was tested in in vitro infection of human PBMCs or coculture of DCs and T-cells. In vivo tumor xenografts were raised in NOD. SCID mice that were later reconstituted with an autologous DCs and T-cells mix primed with an infected or chemovirotherapy (gemcitabine and H-1PV)-treated pancreatic cancer line vaccine. The therapeutic activity of the native and modified viruses was evaluated upon systemic application in pancreatic cancer-bearing immunocompetent Lewis rats. Compared with wt H-1PV, JabCG displayed enhanced immunotherapeutic capacity to activate human immune cells ex vivo (PBMCs or DCs and T-cells isolated from pancreatic cancer patients) with a striking increase in the capacity of the latter cells for suppressing autologous tumorxenografts in NOD.SCID mice. Furthermore, intravenous application of JabCG in immunocompetent rats caused early NK and T-cell infiltration into tumors, elevated IFNÎ³ levels in serum and spleens, and notably prolonged survival, as compared to control-treated animals.
Citation: Grekova SP, Aprahamian M, Giese NA, Bour G, Giese T, et al. (2014) Genomic CpG Enrichment of Oncolytic Parvoviruses as a Potent Anticancer Vaccination Strategy for the Treatment of Pancreatic Adenocarcinoma. J Vaccines Vaccin 5:227. doi: 10.4172/2157-7560.1000227
Last date updated on December, 2020