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- Title
Targeting of melanoma brain metastases using engineered neural stem/progenitor cells.
- Authors
Aboody, Karen S; Najbauer, Joseph; Schmidt, Nils Ole; Yang, Wendy; Wu, Julian K; Zhuge, Yuzheng; Przylecki, Wojciech; Carroll, Rona; Black, Peter M; Perides, George
- 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.
- Publication
Neuro-oncology, 2006, Vol 8, Issue 2, p119
- ISSN
1522-8517
- Publication type
Journal Article
- DOI
10.1215/15228517-2005-012