Send to

Choose Destination
Mol Ther. 2009 Aug;17(8):1465-72. doi: 10.1038/mt.2009.95. Epub 2009 Apr 28.

Recombinant vesicular stomatitis virus transduction of dendritic cells enhances their ability to prime innate and adaptive antitumor immunity.

Author information

Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.


Dendritic cell (DC)-based vaccines are a promising strategy for tumor immunotherapy due to their ability to activate both antigen-specific T-cell immunity and innate immune effector components, including natural killer (NK) cells. However, the optimal mode of antigen delivery and DC activation remains to be determined. Using M protein mutant vesicular stomatitis virus (DeltaM51-VSV) as a gene-delivery vector, we demonstrate that a high level of transgene expression could be achieved in approximately 70% of DCs without affecting cell viability. Furthermore, DeltaM51-VSV infection activated DCs to produce proinflammatory cytokines (interleukin-12, tumor necrosis factor-alpha, and interferon (IFN)alpha/beta), and to display a mature phenotype (CD40(high)CD86(high) major histocompatibility complex (MHC II)(high)). When delivered to mice bearing 10-day-old lung metastatic tumors, DCs infected with DeltaM51-VSV encoding a tumor-associated antigen mediated significant control of tumor growth by engaging both NK and CD8(+) T cells. Importantly, depletion of NK cells completely abrogated tumor destruction, indicating that NK cells play a critical role for this DC vaccine-induced therapeutic outcome. Our findings identify DeltaM51-VSV as both an efficient gene-delivery vector and a maturation agent allowing DC vaccines to overcome immunosuppression in the tumor-bearing host.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center