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

• Published in: European journal of pharmaceutical sciences 2007-04, Vol.30 (5), p.398-405
• Main Authors: Steel, Jason C., Cavanagh, Heather M.A., Burton, Mark A., Abu-Asab, Mones S., Tsokos, Maria, Morris, John C., Kalle, Wouter H.J.
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Adenoviridae - immunology; Adenoviridae - metabolism; Adenovirus; AL complexes; Animals; Antibody Formation; beta-Galactosidase; Biological and medical sciences; Cell Line, Tumor; General pharmacology; Genes, Reporter; Genetic Vectors - immunology; Genetic Vectors - metabolism; Humans; Immuno-protection; Liposomes; Medical sciences; Molecular Conformation; Neutralizing antibodies; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phosphatidylethanolamines - chemistry; Quaternary Ammonium Compounds - chemistry; Rats; Salivary Gland Neoplasms - genetics; Salivary Gland Neoplasms - immunology; Salivary Gland Neoplasms - metabolism; Tissue Distribution; Transduction, Genetic - methods
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2006.12.004

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. 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.