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

Authors :
Hangalapura BN
Timares L
Oosterhoff D
Scheper RJ
Curiel DT
de Gruijl TD
Source :
The journal of gene medicine [J Gene Med] 2012 Jun; Vol. 14 (6), pp. 416-27.
Publication Year :
2012

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.<br /> (Copyright © 2012 John Wiley & Sons, Ltd.)

Details

Language :
English
ISSN :
1521-2254
Volume :
14
Issue :
6
Database :
MEDLINE
Journal :
The journal of gene medicine
Publication Type :
Academic Journal
Accession number :
22228547
Full Text :
https://doi.org/10.1002/jgm.1648