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Marrow-derived stem cells deliver new cytokine to kill brain tumor cells, offer protection

r recapitulates our previous data demonstrating that the neural stem cells ?in this case from bone marrow ?were able to track to the tumor very efficiently and, like a heat-seeking missile, deliver a killer depot," said John S. Yu, M.D., neurosurgeon, co-director of the Comprehensive Brain Tumor Program at the Maxine Dunitz Neurosurgical Institute, and the article's senior author. "We obtained the stem cells from bone marrow, mirroring what we want to do clinically, which is to take bone marrow cells from a patient, make them into neural stem cells, put in the gene of interest and treat the patient."

In this case, the gene of interest produces IL-23, which appears to be very well suited for attacking gliomas. Earlier studies used IL-4, IL-12, and tumor necrosis factor related apoptosis inducing ligand (TRAIL).

"Each cytokine has unique functions. What we want to do is marry the function with the therapeutic response we want to achieve. Interleukin-23 promotes the function of dendritic cells and memory T-cells, important components in an immune response to tumor cells. The earlier cytokines produced good results, but IL-23 is even more potent," Yu said.

"Most anti-tumor gene strategies attempt to deliver genes directly to tumor cells, but gliomas are especially challenging because of their highly invasive and migratory characteristics," said Keith L. Black, M.D., director of the Maxine Dunitz Neurosurgical Institute, director of Cedars-Sinai's Division of Neurosurgery, and co-director of the Comprehensive Brain Tumor Program. "By combining the tumor-tracking properties of bone marrow-derived neural stem cells with interleukin-23, we are able to initiate a very powerful anti-tumor response that tracks to migrating glioma islands and offers long-term protection ?all of which would make this a very attractive therapeutic option."

In the animal study, bone marrow-derived neural stem-like cells (BM-NSC) genetically engineered to produce IL-
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Source:Cedars-Sinai Medical Center


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