title: Targeting of melanoma brain metastases using engineered neural stem/progenitor cells.
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.
authors.affiliation: 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
authors.forename: Karen S
authors.initials: KS
authors.lastname: Aboody
authors.forename: Joseph
authors.initials: J
authors.lastname: Najbauer
authors.forename: Nils Ole
authors.initials: NO
authors.lastname: Schmidt
authors.forename: Wendy
authors.initials: W
authors.lastname: Yang
authors.forename: Julian K
authors.initials: JK
authors.lastname: Wu
authors.forename: Yuzheng
authors.initials: Y
authors.lastname: Zhuge
authors.forename: Wojciech
authors.initials: W
authors.lastname: Przylecki
authors.forename: Rona
authors.initials: R
authors.lastname: Carroll
authors.forename: Peter M
authors.initials: PM
authors.lastname: Black
authors.forename: George
authors.initials: G
authors.lastname: Perides
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000556:secondary* / Q000628:therapy*; D045744:Cell Line, Tumor; D007150:Immunohistochemistry; D008546:Melanoma, Experimental / Q000556:secondary* / Q000628:therapy*; D051379:Mice; D009368:Neoplasm Transplantation; D009474:Neurons / Q000637:transplantation*; D033581:Stem Cell Transplantation