Increased tumor localization and reduced immune response to adenoviral vector formulated with the liposome DDAB/DOPE

Steel, Jason C., Cavanagh, Heather M. A., Burton, Mark A., Abu-Asab, Mones S., Tsokos, Maria, Morris, John C. and Kalle, Wouter H. J. (2007) Increased tumor localization and reduced immune response to adenoviral vector formulated with the liposome DDAB/DOPE. European Journal of Pharmaceutical Sciences, 30 5: 398-405. doi:10.1016/j.ejps.2006.12.004


Author Steel, Jason C.
Cavanagh, Heather M. A.
Burton, Mark A.
Abu-Asab, Mones S.
Tsokos, Maria
Morris, John C.
Kalle, Wouter H. J.
Title Increased tumor localization and reduced immune response to adenoviral vector formulated with the liposome DDAB/DOPE
Journal name European Journal of Pharmaceutical Sciences   Check publisher's open access policy
ISSN 0928-0987
1879-0720
Publication date 2007-04-01
Sub-type Article (original research)
DOI 10.1016/j.ejps.2006.12.004
Open Access Status Not yet assessed
Volume 30
Issue 5
Start page 398
End page 405
Total pages 8
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Language eng
Abstract We aimed to increase the efficiency of adenoviral vectors by limiting adenoviral spread from the target site and reducing unwanted host immune responses to the vector. We complexed adenoviral vectors with DDAB-DOPE liposomes to form adenovirus-liposomal (AL) complexes. AL complexes were delivered by intratumoral injection in an immunocompetent subcutaneous rat tumor model and the immunogenicity of the AL complexes and the expression efficiency in the tumor and other organs was examined. Animals treated with the AL complexes had significantly lower levels of β-galactosidase expression in systemic tissues compared to animals treated with the naked adenovirus (NA) (P < 0.05). The tumor to non-tumor ratio of β-galactosidase marker expression was significantly higher for the AL complex treated animals. NA induced significantly higher titers of adenoviral-specific antibodies compared to the AL complexes (P < 0.05). The AL complexes provided protection (immunoshielding) to the adenovirus from neutralizing antibody. Forty-seven percent more β-galactosidase expression was detected following intratumoral injection with AL complexes compared to the NA in animals pre-immunized with adenovirus. Conclusions: Complexing of adenovirus with liposomes provides a simple method to enhance tumor localization of the vector, decrease the immunogenicity of adenovirus, and provide protection of the virus from pre-existing neutralizing antibodies.
Keyword Adenovirus
AL complexes
Immuno-protection
Liposomes
Neutralizing antibodies
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Wed, 18 Mar 2015, 02:08:11 EST by Jason Steel on behalf of Learning and Research Services (UQ Library)