Targeting of melanoma brain metastases using engineered neural stem/progenitor cells.
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.
Aboody
Karen S
KS
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
Najbauer
Joseph
J
Schmidt
Nils Ole
NO
Yang
Wendy
W
Wu
Julian K
JK
Zhuge
Yuzheng
Y
Przylecki
Wojciech
W
Carroll
Rona
R
Black
Peter M
PM
Perides
George
G
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