The conundrum between immunological memory to adenovirus and their use as vectors in clinical gene therapy.

Details

Serval ID
serval:BIB_D5235ABCB4F3
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Title
The conundrum between immunological memory to adenovirus and their use as vectors in clinical gene therapy.
Journal
Molecular Biotechnology
Author(s)
Perreau M., Kremer E.J.
ISSN
1073-6085 (Print)
ISSN-L
1073-6085
Publication state
Published
Issued date
2006
Volume
34
Number
2
Pages
247-256
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Review , pdf : review
Abstract
In the context of clinical gene transfer using viral vectors, the risk of memory antivector immunity is often poorly appreciated. The immunological past of the patient, the site of injection, and the vector dose will play intertwined and decisive roles in the safety and efficacy of treatment. To circumvent the drawbacks due to the ubiquitous human adenovirus (HAd) memory immunity, we believe that vectors derived from canine adenovirus type 2 (CAV-2) will be more clinically useful than those derived from HAds based, in part, on the potential lack of immunological memory. CAV-2 is not a human pathogen in spite of the approx 100,000 yr of cohabitation of humans with dogs. During the last 8 yr, we found that CAV-2 vectors preferentially transduced neurons in the central nervous system (CNS) of several species, and had a surprisingly efficient level of axoplasmic transport. CAV-2 vectors also lead to greater than 1 yr transgene expression in the immunocompetent rat CNS-without immunosuppression. However, more immediate harm can be caused to a patient via an acute and/or chronic vector-induced cellular infiltration in the CNS than by the normal progression of most neurodegenerative disorders. In this context, we continue to assess the clinical potential of CAV-2. This mini-review addresses our analysis of the interaction of CAV-2 vectors with human memory immunity and monocyte-derived dendritic cells.
Keywords
Adenoviruses, Canine/genetics, Adenoviruses, Canine/immunology, Animals, Antibody Formation, Dendritic Cells/immunology, Dogs, Genetic Therapy/adverse effects, Genetic Vectors/genetics, Genetic Vectors/immunology, Humans, Immunologic Memory, T-Lymphocytes/immunology
Pubmed
Create date
24/10/2014 13:02
Last modification date
20/08/2019 15:54
Usage data