Potent antitumor immunity generated by a CD40-targeted adenoviral vaccine

Basav N. Hangalapura, Dinja Oosterhoff, Jan De Groot, Louis Boon, Thomas Tuẗing, Alfons J. Van Den Eertwegh, Winald R. Gerritsen, Victor W. Van Beusechem, Alexander Pereboev, David T. Curiel, Rik J. Scheper, Tanja D. De Gruijl

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

In situ delivery of tumor-associated antigen (TAA) genes into dendritic cells (DC) has great potential as a generally applicable tumor vaccination approach. Although adenoviruses (Ad) are an attractive vaccine vehicle in this regard, Ad-mediated transduction of DCs is hampered by the lack of expression of the Ad receptor CAR on the DC surface. DC activation also requires interaction of CD40 with its ligand CD40L to generate protective T-cell-mediated tumor immunity. Therefore, to create a strategy to target Ads to DCs in vivo, we constructed a bispecific adaptor molecule with the CAR ectodomain linked to the CD40L extracellular domain via a trimerization motif (CFm40L). By targeting Ad to CD40 with the use of CFm40L, we enhanced both transduction and maturation of cultured bone marrow-derived DCs. Moreover, we improved transduction efficiency of DCs in lymph node and splenic cell suspensions in vitro and in skin and vaccination site-draining lymph nodes in vivo. Furthermore, CD40 targeting improved the induction of specific CD8+ T cells along with therapeutic efficacy in a mouse model of melanoma. Taken together, our findings support the use of CD40-targeted Ad vectors encoding full-length TAA for in vivo targeting of DCs and high-efficacy induction of antitumor immunity.

Original languageEnglish
Pages (from-to)5827-5837
Number of pages11
JournalCancer research
Volume71
Issue number17
DOIs
StatePublished - Sep 1 2011

Fingerprint Dive into the research topics of 'Potent antitumor immunity generated by a CD40-targeted adenoviral vaccine'. Together they form a unique fingerprint.

  • Cite this

    Hangalapura, B. N., Oosterhoff, D., De Groot, J., Boon, L., Tuẗing, T., Van Den Eertwegh, A. J., Gerritsen, W. R., Van Beusechem, V. W., Pereboev, A., Curiel, D. T., Scheper, R. J., & De Gruijl, T. D. (2011). Potent antitumor immunity generated by a CD40-targeted adenoviral vaccine. Cancer research, 71(17), 5827-5837. https://doi.org/10.1158/0008-5472.CAN-11-0804