Targeting of melanoma brain metastases using engineered neural stem/progenitor cells

Neuro-oncology
Karen S AboodyGeorge Perides

Abstract

Brain metastases are an increasingly frequent and serious clinical problem for cancer patients, especially those with advanced melanoma. Given the extensive tropism of neural stem/progenitor cells (NSPCs) for pathological areas in the central nervous system, we expanded investigations to determine whether NSPCs could also target multiple sites of brain metastases in a syngeneic experimental melanoma model. Using cytosine deaminase-expressing NSPCs (CD-NSPCs) and systemic 5-fluorocytosine (5-FC) pro-drug administration, we explored their potential as a cell-based targeted drug delivery system to disseminated brain metastases. Our results indicate a strong tropism of NSPCs for intracerebral melanoma metastases. Furthermore, in our therapeutic paradigm, animals with established melanoma brain metastasis received intracranial implantation of CD-NSPCs followed by systemic 5-FC treatment, resulting in a significant (71%) reduction in tumor burden. These data provide proof of principle for the use of NSPCs for targeted delivery of therapeutic gene products to melanoma brain metastases.

References

Jan 1, 1994·Annals of Surgical Oncology·S SahaC Sutherland
Mar 18, 2000·Cancer Metastasis Reviews·I J FidlerT Fujimaki
Mar 31, 2000·Nature Medicine·S BenedettiG Finocchiaro
Aug 10, 2000·Molecular Therapy : the Journal of the American Society of Gene Therapy·U HerrlingerX O Breakefield
Nov 9, 2000·Proceedings of the National Academy of Sciences of the United States of America·K S AboodyE Y Snyder
Apr 30, 2003·Cancer Gene Therapy·Vincenza BarresiDaniele Filippo Condorelli
Jun 6, 2003·Oncogene·Michael Streit, Michael Detmar
Jun 25, 2003·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M WestphalM de Wit
Sep 3, 2003·Nature Reviews. Cancer·Mark E Dudley, Steven A Rosenberg
Sep 4, 2003·The Cancer Journal·Stephen YipEvan Y Snyder
Sep 19, 2003·Neuroimaging Clinics of North America·Alf HutterRobert C McKinstry
Oct 31, 2003·Cancer Treatment Reviews·Roy A Patchell
May 5, 2004·The Journal of Clinical Investigation·Lixin SunHoward A Fine
May 18, 2004·The Journal of Biological Chemistry·Gaëlle LefevreFrédéric Mascarelli
May 22, 2004·Neoplasia : an International Journal for Oncology Research·Moneeb EhteshamJohn S Yu
Nov 4, 2004·Journal of the National Cancer Institute·Matus StudenyMichael Andreeff
Apr 19, 2005·Cancer Research·Akira NakamizoFrederick F Lang
Jul 23, 2005·Neoplasia : an International Journal for Oncology Research·Nils Ole SchmidtRona S Carroll

❮ Previous
Next ❯

Citations

Jul 16, 2011·Molecular Pharmaceutics·Marina CihovaCestmir Altaner
Feb 4, 2010·ACS Nano·Hao ChengDaniel G Anderson
Mar 29, 2008·Gene Therapy·K S AboodyM K Danks
Jan 8, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kyeung Min JooDo-Hyun Nam
Oct 22, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ilaria T CavarrettaCestmir Altaner
Jun 1, 2012·Tissue Engineering. Part a·Yee-Shuan Lee, Treena Livingston Arinzeh
May 10, 2013·Science Translational Medicine·Karen S AboodyJana Portnow
Dec 22, 2006·PloS One·Karen S AboodyMary K Danks
Aug 30, 2007·Journal of Zhejiang University. Science. B·Borislav D DimitrovMariana I Rachkova
May 25, 2011·World Journal of Stem Cells·Dharmendra Kumar MauryaDeryl Troyer
Jul 27, 2012·Therapeutic Delivery·Carmen Gutiérrez MillánJosé M Lanao
Apr 1, 2011·Therapeutic Delivery·Joel C SunshineJordan J Green
Jun 4, 2010·Stem Cell Reviews and Reports·Seung U Kim
Nov 3, 2011·Expert Reviews in Molecular Medicine·Ivan PachecoVictor Tron
Nov 30, 2011·Current Opinion in Supportive and Palliative Care·May N TsaoMinesh P Mehta
Aug 30, 2008·Expert Opinion on Drug Metabolism & Toxicology·Jason M HatfieldPhilip M Potter
Dec 19, 2012·Translational Research : the Journal of Laboratory and Clinical Medicine·Andrea M Murphy, Samuel D Rabkin
Dec 20, 2011·Biochemical and Biophysical Research Communications·Jae Ho KimKyung Gi Cho
Nov 27, 2010·Neurosurgery Clinics of North America·Muhammad M Abd-El-BarrGanesh Rao
Mar 23, 2010·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Joana Monteiro, Riccardo Fodde
Oct 30, 2015·Stem Cell Research·Nikita G AlexiadesAtique U Ahmed
Sep 22, 2009·Cancer Letters·Miroslava MatuskovaLucia Kucerova
May 27, 2008·Cancer Letters·Cestmir Altaner
Nov 21, 2007·Current Opinion in Biotechnology·Jason Sharp, Hans S Keirstead
Dec 17, 2008·Biotechnology Journal·Carsten W Lederer, Niovi Santama

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.