Neural progenitor cell-mediated delivery of interferon beta improves neuroblastoma response to cyclophosphamide.

Annals of Surgical Oncology
Thomas L SimsAndrew M Davidoff

Abstract

We have shown that continuous systemic delivery of interferon beta (IFN-beta) remodels dysfunctional tumor vasculature, thereby improving tumor perfusion and enhancing delivery and efficacy of chemotherapeutic drugs. We hypothesized that because of their inherent tumor tropism, neural progenitor cells (NPCs) engineered to express IFN-beta could also effect maturation of tumor vasculature without generating high systemic levels of IFN-beta. Mice with luciferase-expressing disseminated human neuroblastoma were divided into four groups of equal tumor burden by bioluminescence imaging: (1) untreated controls; (2) NPC-IFN-beta only; (3) cyclophosphamide (CTX) only; and (4) NPC-IFN-beta in combination with CTX. Two million NPC-IFN-beta cells were administered twice, 7 days apart, starting 21 days after tail vein administration of tumor cells. CTX was administered every 6 days for three doses. Mice were killed at 6 weeks, livers and kidneys weighed, and tumor removed for immunohistochemical staining for endothelial cells (CD34), pericytes (alpha-SMA), apoptosis (TUNEL [terminal deoxynucleotidyl transferase dUTP nick-end labeling]), and diI-labeled NPCs. Fluorescent-labeled NPCs confirmed localization of these cells to tumors. The alph...Continue Reading

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Citations

Mar 12, 2009·Journal of Cellular Biochemistry·Lars M Wagner, Mary K Danks
Apr 2, 2013·Gene·Guillaume ColletClaudine Kieda

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