Intravascular administration of tumor tropic neural progenitor cells permits targeted delivery of interferon-bb and restricts tumor growth in a murine model of disseminated neuroblastoma Paxton V. Dickson a,b , John B. Hamner a,b , Rebecca A. Burger c , Elizabeth Garcia f , Annastasia A. Ouma e , Seung U. Kim d , Catherine Y.C. Ng a , John T. Gray e , Karen S. Aboody f , Mary K. Danks c , Andrew M. Davidoff a,b, * a Department of Surgery, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA b Department of Surgery, The University of Tennessee–Memphis Health Science Center, Memphis, TN 38163, USA c Department of Molecular Pharmacology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA d Division of Neurology, UBC Hospital, University of British Columbia, Vancouver, Canada V6T 2B5 e Division of Experimental Hematology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA f Divisions of Hematology and Hematopoietic Cell Transplantation and Neurosciences and Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA Abstract Background: Interferon-b (IFN-b) has potent antitumor activity; however, systemic toxicity has limited its clinical use. We investigated the potential of targeted delivery using tumor-tropic neural progenitor cells (NPCs) transduced to express human IFN-b (hIFN-b). Methods: Disseminated neuroblastoma was established in SCID mice by tail vein injection of tumor cells. Fourteen days after tumor cell inoculation, systemic disease was confirmed with bioluminescence imaging (BLI). Mice were then treated by intravenous injection of human F3.C1 NPCs that had been transduced with a replication deficient adenovirus to overexpress hIFN-b (F3-IFN-b). Two injections were given: the first at 14 days and the second at 28 days following tumor cell injection. Control mice received NPCs transduced with empty vector adenovirus at the same time points. Progression of disease was monitored using BLI. At sacrifice, organ weights and histology further evaluated tumor burden. Results: After initiation of therapy, BLI demonstrated a significant decrease in the rate of disease progression in mice receiving F3-IFN-b. At necropsy, control mice had bulky tumor replacing the liver and kidneys, as well as extensive retroperitoneal and mediastinal adenopathy. Impressively, these sites within mice receiving F3-IFN-b therapy appeared grossly normal with the exception of small nodules within the kidneys of some of the F3-IFN-b–treated mice. The accumulation of F3.C1 cells within sites of tumor growth was confirmed by fluorescence imaging. Importantly, systemic levels of hIFN-b in the treated mice remained below detectable levels. 0022-3468/$ – see front matter D 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2006.09.050 Presented at the 37th Annual Meeting of the American Pediatric Surgical Association, May 20–24, 2006, Hilton Head, SC. * Corresponding author. Department of Surgery, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA. Tel.: +1 901 495 4060; fax: +1 901 495 2176. E-mail address: andrew.davidoff@stjude.org (A.M. Davidoff). Index words: Interferon; Neural progenitor cells; Neuroblastoma Journal of Pediatric Surgery (2007) 42, 48–53 www.elsevier.com/locate/jpedsurg