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

Jeanette E. Boudreau, Byram W. Bridle, Kyle B. Stephenson, Kristina M. Jenkins, Jérôme Brunellière, Jonathan L. Bramson, Brian D. Lichty, Yonghong Wan

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

67 Citas (Scopus)

Resumen

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 (ΔM51-VSV) as a gene-delivery vector, we demonstrate that a high level of transgene expression could be achieved in ∼70% of DCs without affecting cell viability. Furthermore, ΔM51-VSV infection activated DCs to produce proinflammatory cytokines (interleukin-12, tumor necrosis factor-α, and interferon (IFN)α/β), and to display a mature phenotype (CD40highCD86high major histocompatibility complex (MHC II)high). When delivered to mice bearing 10-day-old lung metastatic tumors, DCs infected with ΔM51-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 ΔM51-VSV as both an efficient gene-delivery vector and a maturation agent allowing DC vaccines to overcome immunosuppression in the tumor-bearing host.

Idioma originalEnglish
Páginas (desde-hasta)1465-1472
Número de páginas8
PublicaciónMolecular Therapy
Volumen17
N.º8
DOI
EstadoPublished - 2009
Publicado de forma externa

Nota bibliográfica

Funding Information:
We gratefully acknowledge the technical assistance of Natasha Kazdhan for production of the recombinant VSV vectors and Stephen Hanson for the IFN bioassay. This work was supported by the Ontario Cancer Research Network and grants to Y.W. from the Canadian Institutes of Health Research (MOP-67066) and B.D.L. from the Canadian Cancer Society (017103). J.E.B. is supported by studentships from the Natural Sciences and Engineering Research Council of Canada.

ASJC Scopus Subject Areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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