CD40-targeted adenoviral cancer vaccines: The long and winding road to the clinic

Basav N. Hangalapura, Laura Timares, Dinja Oosterhoff, Rik J. Scheper, David T. Curiel, Tanja D. de Gruijl

Research output: Contribution to journalReview articlepeer-review

18 Scopus citations

Abstract

The ability of dendritic cells (DCs) to orchestrate innate and adaptive immune responses has been exploited to develop potent anti-cancer immunotherapies. Recent clinical trials exploring the efficacy of ex vivo modified autologous DC-based vaccines have reported some promising results. However, in vitro generation of autologous DCs for clinical administration, their loading with tumor associated antigens (TAAs) and their activation, is laborious and expensive, and, as a result of inter-individual variability in the personalized vaccines, remains poorly standardized. An attractive alternative approach is to load resident DCs in vivo by targeted delivery of TAAs, using viral vectors and activating them simultaneously. To this end, we have constructed genetically-modified adenoviral (Ad) vectors and bispecific adaptor molecules to retarget Ad vectors encoding TAAs to the CD40 receptor on DCs. Pre-clinical human and murine studies conducted so far have clearly demonstrated the suitability of a 'two-component' (i.e. Ad and adaptor molecule) configuration for targeted modification of DCs in vivo for cancer immunotherapy. This review summarizes recent progress in the development of CD40-targeted Ad-based cancer vaccines and highlights pre-clinical issues in the clinical translation of this approach.

Original languageEnglish
Pages (from-to)416-427
Number of pages12
JournalJournal of Gene Medicine
Volume14
Issue number6
DOIs
StatePublished - Jun 2012

Keywords

  • Adenovirus
  • CD40
  • Cancer immunotherapy
  • DC
  • In vivo targeting

Fingerprint

Dive into the research topics of 'CD40-targeted adenoviral cancer vaccines: The long and winding road to the clinic'. Together they form a unique fingerprint.

Cite this