Increased tumor localization and reduced immune response to adenoviral vector formulated with the liposome DDAB/DOPE.
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 beta-galactosidase expression in systemic tissues compared to animals treated with the naked adenovirus (NA) (P<0.05). The tumor to non-tumor ratio of beta-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 beta-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.
Steel
Jason C
JC
School of Biomedical Science, Charles Sturt University, P.O. Box 588, Wagga Wagga 2678, Australia. jason_steel@nih.gov
Cavanagh
Heather M A
HM
Burton
Mark A
MA
Abu-Asab
Mones S
MS
Tsokos
Maria
M
Morris
John C
JC
Kalle
Wouter H J
WH
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000917:Antibody Formation; D045744:Cell Line, Tumor; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008081:Liposomes; D008968:Molecular Conformation; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D051381:Rats; D012468:Salivary Gland Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014018:Tissue Distribution; D014161:Transduction, Genetic / Q000379:methods*; D001616:beta-Galactosidase
D008081:Liposomes; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; C046112:didodecyldimethylammonium; C094877:dioleoyl phosphatidylethanolamine; D001616:beta-Galactosidase