Harnessing Oncolytic Virus-mediated Antitumor Immunity in an Infected Cell Vaccine

Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
Molecular Therapy (Impact Factor: 6.23). 07/2012; 20(9):1791-9. DOI: 10.1038/mt.2012.128
Source: PubMed


Treatment of permissive tumors with the oncolytic virus (OV) VSV-Δ51 leads to a robust antitumor T-cell response, which contributes to efficacy; however, many tumors are not permissive to in vivo treatment with VSV-Δ51. In an attempt to channel the immune stimulatory properties of VSV-Δ51 and broaden the scope of tumors that can be treated by an OV, we have developed a potent oncolytic vaccine platform, consisting of tumor cells infected with VSV-Δ51. We demonstrate that prophylactic immunization with this infected cell vaccine (ICV) protected mice from subsequent tumor challenge, and expression of granulocyte-monocyte colony stimulating factor (GM-CSF) by the virus (VSVgm-ICV) increased efficacy. Immunization with VSVgm-ICV in the VSV-resistant B16-F10 model induced maturation of dendritic and natural killer (NK) cell populations. The challenge tumor is rapidly infiltrated by a large number of interferon γ (IFNγ)-producing T and NK cells. Finally, we demonstrate that this approach is robust enough to control the growth of established tumors. This strategy is broadly applicable because of VSV's extremely broad tropism, allowing nearly all cell types to be infected at high multiplicities of infection in vitro, where the virus replication kinetics outpace the cellular IFN response. It is also personalized to the unique tumor antigen(s) displayed by the cancer cell.

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    • "Previous research has demonstrated the importance of the adaptive immune response in determining cures with OV. T-lymphocytes in particular play a central role in the development of the oncolytic virus/VSVΔM51 mediated adaptive antitumor immunity [21, 22]. The lack of cures in our animal model is likely as a result of using an immune compromised mouse model in order to support the growth of human EWS cells. "
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    • "It is also possible to take advantage of this vaccine effect by infecting cancer cells ex vivo and re-injecting the inactivated " oncolysate " to generate prophylactic and even therapeutic anticancer immune responses. The resulting up-regulation of MHCs and co-regulatory factors and presentation of tumor antigens at the surface of OV infected cells as well as the presence of immunestimulating virus is thought to be at the root of this effect (Lemay et al., 2012). Overall, these studies emphasize the important role of antigen expression/presentation in OV-stimulated anti-tumoral responses. "
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