A Th1-inducing adenoviral vaccine for boosting adoptively transferred T cells

Mol Ther. 2011 Jan;19(1):211-7. doi: 10.1038/mt.2010.223. Epub 2010 Oct 19.


Although the benefits of adoptive T-cell therapy can be increased by prior lymphodepletion of the recipient, this process usually requires chemotherapy or radiation. Vaccination with antigens to which the transferred T cells respond should be a less toxic means of enhancing their activity, but to date such vaccines have not been effective. We, therefore, determined which characteristics an adenoviral vaccine has to fulfill to optimally activate and expand adoptively transferred antigen-specific T cells in vivo. We evaluated (i) antigen, (ii) flagellin, a Toll-like receptor (TLR) 5 ligand, and (iii) an inhibitor of the antigen-presenting attenuator A20. Vaccination of mice before T-cell transfer with a vaccine that contained all three components dramatically enhanced the effector function of ovalbumin (OVA)-specific T cells as judged by the regression of established B16-OVA tumors compared to one- and two-component vaccines. Immunization with the three-component vaccine induced a strong Th1 environment, which was critical for the observed synergy and proved as effective as cytoxan-induced lymphodepletion in enhancing in vivo T-cell expansion. Thus, the combination of our vaccine with T-cell therapy has the potential to enhance and broaden adoptive cellular immunotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / immunology*
  • Animals
  • Antigen Presentation / immunology
  • Antigens / immunology
  • Cancer Vaccines / immunology*
  • Cell Line
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Flagellin / genetics
  • Immunization, Secondary / methods
  • Immunotherapy, Adoptive / methods*
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / therapy
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Ovalbumin / immunology
  • RNA, Small Interfering / genetics
  • T-Lymphocytes / immunology*
  • Th1 Cells / immunology*
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / metabolism
  • Viral Vaccines / immunology*


  • Antigens
  • Cancer Vaccines
  • RNA, Small Interfering
  • Vaccines, Synthetic
  • Viral Vaccines
  • Flagellin
  • Ovalbumin