Genomic CpG Enrichment of Oncolytic Parvoviruses as a Potent Anticancer Vaccination Strategy for the Treatment of Pancreatic Adenocarcinoma
Svitlana P. Grekova1, Marc Aprahamian2, Nathalia A. Giese3, Gaetan Bour2, Thomas Giese4, Annabel Grewenig1, Barbara Leuchs1, Rita Hörlein1, Anette Heller3, Assia L. Angelova1, Jean Rommelaere1 and Zahari Raykov1*
- *Corresponding Author:
- Zahari Raykov
Applied Tumor Virology Programme, Divisions F010
German Cancer Research Centre (DKFZ), Heidelberg, Germany
E-mail: [email protected]
Received date: March 19, 2014; Accepted date: April 24, 2014; Published date: April 26, 2014
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
Copyright: © 2014 RaykovZ. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: 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. Methods: 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. Results: 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 IFNγ levels in serum and spleens, and notably prolonged survival, as compared to control-treated animals. Conclusion: Taken together, data indicate that CpG-enrichment of OVs represents a potent strategy to enhance their immunotherapeutic properties.