Journal
MOLECULAR THERAPY
Volume 17, Issue 8, Pages 1465-1472Publisher
CELL PRESS
DOI: 10.1038/mt.2009.95
Keywords
-
Categories
Funding
- Ontario Cancer Research Network
- Canadian Institutes of Health Research [MOP- 67066]
- Canadian Cancer Society [017103]
- Natural Sciences and Engineering Research Council of Canada
Ask authors/readers for more resources
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(Delta M51-VSV) as a gene-delivery vector, we demonstrate that a high level of transgene expression could be achieved in similar to 70% of DCs without affecting cell viability. Furthermore, Delta M51-DCs 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 Delta M51-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 Delta 51- VSV as both an efficient gene- delivery vector and a maturation agent allowing DC vaccines to overcome immunosuppression in the tumor- bearing host.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available