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Neuro Oncol. 2006 Apr;8(2):119-26. Epub 2006 Mar 8.

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

Author information

1
Divisions of Hematology and Hematopoietic Cell Transplantation and Neurosciences and Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010-3000, USA. kaboody@coh.org

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.

PMID:
16524944
PMCID:
PMC1871940
DOI:
10.1215/15228517-2005-012
[Indexed for MEDLINE]
Free PMC Article
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