Transplantation of prodrug-converting neural progenitor cells for brain tumor therapy.
Since neural progenitor cells can engraft stably into brain tumors and differentiate along the neuronal and glial line, we tested the hypothesis that transplanted cytosine deaminase (CD)-expressing ST14A cells (an immortalized neural progenitor cell line) can convert locally 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU) and produce a regression of glioma tumors. ST14A, retrovirally transduced with the E. coli CD gene, showed a strong bystander effect on glioma cells as assessed by in vitro assay. Intracerebral injection of C6 glioma cells generated a rapidly growing tumoral mass. DiI prelabeled ST14A, coinjected into the rat brain with C6 glioma cells, survived in the tumoral mass up to 10 days and their number was not affected by in vivo 5-FC treatment. In contrast, a significant decrease of the glioma tumoral mass (-50%) was observed in 5-FC-treated rats. 5-FC had no effect on the tumor in the absence of CD-expressing ST14A cells. Our results support the feasibility of systems based on intratumoral transplantation of prodrug-converting cells for brain tumor therapy.
Department of Chemical Sciences, University of Catania, Italy.
Vincenza
V
Barresi
Natale
N
Belluardo
Simonetta
S
Sipione
Giuseppa
G
Mudò
Elena
E
Cattaneo
Daniele Filippo
DF
Condorelli
D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002478:Cells, Cultured; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology; D005437:Flucytosine / Q000378:metabolism; D005472:Fluorouracil / Q000378:metabolism; D015316:Genetic Therapy; D005910:Glioma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D009474:Neurons / Q000166:cytology; D011355:Prodrugs / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000201:enzymology*; D014162:Transfection
D011355:Prodrugs; D005437:Flucytosine; D043525:Cytosine Deaminase; D005472:Fluorouracil