636. Antitumoral Activity Mediated by a Lipid- Based Gene Delivery System Containing Therapeutic Genes
Authors: Henrique Faneca, António Cabrita, Sérgio Simões, Maria Pedroso de Lima
Journal: Molecular Therapy (2006)

Cationic liposome/DNA complexes have been extensively studied aiming at developing appropriate non-viral gene delivery systems. We have previously reported that association of albumin to complexes, containing the new cationic lipid 1-palmitoyl-2-oleoyl- sn-glycero-3-ethylphosphocholine (EPOPC) and cholesterol (Chol), prepared at the (4/1) (+/−) lipid/DNA charge ratio, strongly enhances their biological activity, even in the presence of serum. Therefore, in the present work, we used albumin-associated complexes with this composition to evaluate, in an animal model bearing a subcutaneous TSA tumor, the antitumoral efficacy of two gene therapy strategies: immuno-gene therapy, mediated by IL-12 gene expression, and "suicide" gene therapy, mediated by HSV-tk gene expression followed by ganciclovir (GCV) treatment.Our data show that intratumoral administration of the albumin-associated complexes containing the plasmid encoding IL-12 results in a significant antitumoral effect, as demonstrated by the smaller tumor size, the higher T-lymphocyte tumor infiltration and the more extensive tumor necrotic and hemorrhagic areas, as compared to that observed in tumors of animals treated with control complexes (the same formulation containing a plasmid encoding luciferase gene). On the other hand, the application of the "suicide" gene therapy strategy results in a significant antitumoral activity, which is similar to that achieved with the immuno-gene therapy strategy, although involving different antineoplastic mechanisms.Overall, our results demonstrate that albumin-associated complexes can efficiently mediate intratumoral delivery of therapeutic genes, thus leading to a significant antitumoral effect. Cationic liposome/DNA complexes have been extensively studied aiming at developing appropriate non-viral gene delivery systems. We have previously reported that association of albumin to complexes, containing the new cationic lipid 1-palmitoyl-2-oleoyl- sn-glycero-3-ethylphosphocholine (EPOPC) and cholesterol (Chol), prepared at the (4/1) (+/−) lipid/DNA charge ratio, strongly enhances their biological activity, even in the presence of serum. Therefore, in the present work, we used albumin-associated complexes with this composition to evaluate, in an animal model bearing a subcutaneous TSA tumor, the antitumoral efficacy of two gene therapy strategies: immuno-gene therapy, mediated by IL-12 gene expression, and "suicide" gene therapy, mediated by HSV-tk gene expression followed by ganciclovir (GCV) treatment. Our data show that intratumoral administration of the albumin-associated complexes containing the plasmid encoding IL-12 results in a significant antitumoral effect, as demonstrated by the smaller tumor size, the higher T-lymphocyte tumor infiltration and the more extensive tumor necrotic and hemorrhagic areas, as compared to that observed in tumors of animals treated with control complexes (the same formulation containing a plasmid encoding luciferase gene). On the other hand, the application of the "suicide" gene therapy strategy results in a significant antitumoral activity, which is similar to that achieved with the immuno-gene therapy strategy, although involving different antineoplastic mechanisms. Overall, our results demonstrate that albumin-associated complexes can efficiently mediate intratumoral delivery of therapeutic genes, thus leading to a significant antitumoral effect.