Programmable insect cell carriers for systemic delivery of integrated cancer biotherapy

• Published in: Journal of controlled release 2015-12, Vol.220 (Pt A), p.210-221
• Main Authors: Roy, D.G., Power, A.T., Bourgeois-Daigneault, M.C., Falls, T., Ferreira, L., Stern, A., Tanese de Souza, C., McCart, J.A., Stojdl, D.F., Lichty, B.D., Atkins, H., Auer, R.C., Bell, J.C., Le Boeuf, F.
• Format: Article
• Language: English
• Subjects: Animals; Cancer biotherapeutics; Cell carriers; Cercopithecus aethiops; Drosophila melanogaster - cytology; Drosophila melanogaster - genetics; Drosophila melanogaster - immunology; Drosophila melanogaster - virology; Female; Gene delivery; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Viral; Genetic Therapy - methods; HeLa Cells; HT29 Cells; Humans; Immunocompetence; Lung Neoplasms - genetics; Lung Neoplasms - immunology; Lung Neoplasms - pathology; Lung Neoplasms - therapy; Lung Neoplasms - virology; MCF-7 Cells; Mice, Inbred BALB C; Oncolytic Virotherapy - methods; Oncolytic viruses; Oncolytic Viruses - genetics; Oncolytic Viruses - immunology; Oncolytic Viruses - pathogenicity; Systemic delivery; Time Factors; Transfection; Tumor Burden; Vero Cells; Xenograft Model Antitumor Assays
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2015.10.030

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. [Display omitted]