The use of neural stem cells in cancer gene therapy: predicting the path to the clinic
- PMID: 20886386
- PMCID: PMC2958255
The use of neural stem cells in cancer gene therapy: predicting the path to the clinic
Abstract
Gene therapy is a novel means of anticancer treatment that has led to preliminary positive results in the preclinical setting, as well as in clinical trials; however, successful clinical application of this approach has been hampered by the inability of gene delivery systems to target tumors and to deliver a therapeutic payload to disseminated tumor foci efficiently. Along with viral vector systems, various mammalian cells with tropism for tumor cells have been considered as vehicles for delivery of anticancer therapeutics. The discovery of the inherent tumor-tropic properties of neural stem cells (NSCs) has provided a unique opportunity to develop targeted therapies that use NSCs as a vehicle to track invasive tumor cells and deliver anticancer agents selectively to diseased areas. Many in vivo and in vitro studies have demonstrated that the targeted migration of NSCs to infiltrative brain tumors, including malignant glioma, provides a potential therapeutic approach. In this review, the development of NSCs as targeted carriers for anticancer gene therapy is discussed, and barriers in the path to the clinic, as well as approaches to overcoming such barriers are presented.
References
-
-
Brustle O, Spiro AC, Karram K, Choudhary K, Okabe S, McKay RD. In vitro-generated neural precursors participate in mammalian brain development. Proc Natl Acad Sci USA. 1997;94(26):14809–14814. • An important paper establishing the feasibility of the in vitro manipulation of NSCs and their transplantation into the mammalian brain.
-
-
-
Aboody KS, Brown A, Rainov NG, Bower KA, Liu S, Yang W, Small JE, Herrlinger U, Ourednik V, Black PM, Breakefield XO, et al. Neural stem cells display extensive tropism for pathology in adult brain: Evidence from intracranial gliomas. Proc Natl Acad Sci USA. 2000;97(23):12846–12851. •• Presents the first suicide gene therapy approach to NSC-mediated targeted therapy for glioblastoma. Identified robust tumor-targeted migration from distant sites, via different methods of administration and to disseminated tumor foci.
-
-
-
Benedetti S, Pirola B, Pollo B, Magrassi L, Bruzzone MG, Rigamonti D, Galli R, Selleri S, Di Meco F, De Fraja C, Vescovi A, et al. Gene therapy of experimental brain tumors using neural progenitor cells. Nat Med. 2000;6(4):447–450. •• The first study to use NSCs as vectors for the targeted delivery of therapeutic agents. Highlights both the tumor tropism of NSCs and the feasibility of their use for localized drug delivery.
-
-
- Muller FJ, Snyder EY, Loring JF. Gene therapy: Can neural stem cells deliver? Nat Rev Neurosci. 2006;7(1):75–84. - PubMed
Publication types
MeSH terms
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical