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J Control Release ; 220(Pt A): 210-221, 2015 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-26482080

RESUMEN

Due to cancer's genetic complexity, significant advances in the treatment of metastatic disease will require sophisticated, multi-pronged therapeutic approaches. Here we demonstrate the utility of a Drosophila melanogaster cell platform for the production and in vivo delivery of multi-gene biotherapeutic systems. We show that cultured Drosophila S2 cell carriers can stably propagate oncolytic viral therapeutics that are highly cytotoxic for mammalian cancer cells without adverse effects on insect cell viability or gene expression. Drosophila cell carriers administered systemically to immunocompetent animals trafficked to tumors to deliver multiple biotherapeutics with little apparent off-target tissue homing or toxicity, resulting in a therapeutic effect. Cells of this Dipteran invertebrate provide a genetically tractable platform supporting the integration of complex, multi-gene biotherapies while avoiding many of the barriers to systemic administration of mammalian cell carriers. These transporters have immense therapeutic potential as they can be modified to express large banks of biotherapeutics with complementary activities that enhance anti-tumor activity.


Asunto(s)
Drosophila melanogaster/genética , Terapia Genética/métodos , Neoplasias Pulmonares/terapia , Viroterapia Oncolítica/métodos , Virus Oncolíticos/genética , Animales , Chlorocebus aethiops , Drosophila melanogaster/citología , Drosophila melanogaster/inmunología , Drosophila melanogaster/virología , Femenino , Regulación Neoplásica de la Expresión Génica , Regulación Viral de la Expresión Génica , Células HT29 , Células HeLa , Humanos , Inmunocompetencia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/virología , Células MCF-7 , Ratones Endogámicos BALB C , Virus Oncolíticos/inmunología , Virus Oncolíticos/patogenicidad , Factores de Tiempo , Transfección , Carga Tumoral , Células Vero , Ensayos Antitumor por Modelo de Xenoinjerto
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