The influence of innate and pre‐existing immunity on adenovirus therapy

AK Zaiss, HB Machado… - Journal of cellular …, 2009 - Wiley Online Library
AK Zaiss, HB Machado, HR Herschman
Journal of cellular biochemistry, 2009Wiley Online Library
Abstract Recombinant adenovirus serotype 5 (Ad5) vectors have been studied extensively in
preclinical gene therapy models and in a range of clinical trials. However, innate immune
responses to adenovirus vectors limit effectiveness of Ad5 based therapies. Moreover,
extensive pre‐existing Ad5 immunity in human populations will likely limit the clinical utility
of adenovirus vectors, unless methods to circumvent neutralizing antibodies that bind virus
and block target cell transduction can be developed. Furthermore, memory T cell and …
Abstract
Recombinant adenovirus serotype 5 (Ad5) vectors have been studied extensively in preclinical gene therapy models and in a range of clinical trials. However, innate immune responses to adenovirus vectors limit effectiveness of Ad5 based therapies. Moreover, extensive pre‐existing Ad5 immunity in human populations will likely limit the clinical utility of adenovirus vectors, unless methods to circumvent neutralizing antibodies that bind virus and block target cell transduction can be developed. Furthermore, memory T cell and humoral responses to Ad5 are associated with increased toxicity, raising safety concerns for therapeutic adenovirus vectors in immunized hosts. Most preclinical studies have been performed in naļve animals; although pre‐existing immunity is among the greatest hurdles for adenovirus therapies, it is also one of the most neglected experimentally. Here we summarize findings using adenovirus vectors in naļve animals, in Ad‐immunized animals and in clinical trials, and review strategies proposed to overcome innate immune responses and pre‐existing immunity. J. Cell. Biochem. 108: 778–790, 2009. © 2009 Wiley‐Liss, Inc.
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