Liposomal enhancement of the antitumor activity of conditionally replication-competent adenoviral plasmids.
Mol Ther
; 9(4): 489-95, 2004 Apr.
Article
em En
| MEDLINE
| ID: mdl-15093179
ABSTRACT
Many human tumors have a functional deficiency in p53. Numerous studies have taken advantage of this phenomenon to use a conditionally replication-competent adenovirus (Ad dl1520) that will grow in and lyse tumor cells while sparing normal tissues. However, success has been limited, in part due to difficulties in reaching a sufficiently high proportion of tumor cells. Preexisting or developing immune responses directed toward viral proteins further decrease the efficacy of the approach. We have developed a liposome-encapsulated conditionally replication-competent plasmid based on the dl1520 virus. Like the parent virus, this plasmid generates infectious particles following transfection of p53-defective, but not p53-wild-type tumor cells, but unlike the parent virus it is able to infect CAR-negative tumor cells. The antitumor efficacy of this infectious plasmid was demonstrated in mice with xenografted human tumors, in which it was active after both local and intravenous administration for subcutaneous tumors and following intravenous administration for disseminated malignancy. Activity was retained systemically, even in the presence of neutralizing antibody. Such liposomally encapsulated conditionally replication-competent plasmids may complement the use of conventional viral particles, particularly in settings in which liver uptake of adenoviral vector is undesirable or there are problematic inhibitory effects from humoral immune responses.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plasmídeos
/
Terapia Genética
/
Adenoviridae
/
Lipossomos
/
Neoplasias
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Ther
Ano de publicação:
2004
Tipo de documento:
Article