Gene-Engineered Neural Stem/Progenitor Cells Demonstrate Tumor-Selective Migration and Antitumor Effects in Glioma
Recent research from the United States has presented fresh data on cancer gene therapy, particularly in the treatment of glioblastoma multiforme (GBM). The study, led by J. Mercapide and colleagues from the University of South Alabama, Cancer Institute, investigated the use of primary neural stem/progenitor cells (NSPC) as a potential therapeutic strategy for GBM. The researchers aimed to develop new adjuvant treatments for this aggressive brain cancer, which has a generally poor prognosis after surgical tumor resection.
Key Takeaways:
- Primary neural stem/progenitor cells (NSPC) exhibited tropism towards medium conditioned by glioma cells, indicating their potential for targeted therapy.
- NSPC were attracted to and fused with tumor cells in adherent low-cell density co-culture, with NSPC-tumor hybrids representing 2-3% of the total cell population.
- The NSPC were coinjected into mouse brain with GBM cells, expressing cyclophosphamide (CPA)-activating enzyme cytochrome p450 2B6, which catalyzes CPA prodrug transformation into membrane diffusible DNA-alkylating metabolites.
- Upon CPA administration, NSPC containing CYP2B6 elicited substantial impairment of tumor growth, indicating a potential therapeutic effect.
- Directed migration of primary NSPC corresponded closely with intracerebral and tumoral pattern of expression of vascular endothelial growth factor, a motility factor for NSPC.
- The researchers concluded that therapeutic gene delivery mediated by primary NSPC is a potentially valid strategy for treatment of high-grade gliomas.
Statistics:
- 2-3% of total cell population represented NSPC-tumor hybrids after 24-48 hr of co-culture in suspension.
- NSPC elicited substantial impairment of tumor growth when expressing CPA-activating enzyme CYP2B6.
- Directed migration of primary NSPC corresponded closely with intracerebral and tumoral pattern of expression of vascular endothelial growth factor.
Sources:
- Primary gene-engineered neural stem/progenitor cells demonstrate tumor-selective migration and antitumor effects in glioma. International Journal of Cancer Journal International Du Cancer, 2010;126(5):1206-15.
- The Mitchell Cancer Institute, University of South Alabama (http://www.southalabama.edu/mit/)
- Cancer Gene Therapy, a publication from NewsRx.com (http://www.newsrx.com/)