Stem Cell-Conventional Treatment Combo Offers New Hope in Fighting Deadly Brain Cancer


A new type of treatment that combines neural stem cells with conventional cancer fighting therapies shows promise in animal studies for the most common and deadliest form of adult brain cancer — glioblastoma multiforme (GBM). The details are revealed in a groundbreaking study led by Maciej Lesniak, M.D., that appeared in the journal STEM CELLS Translational Medicine.

“In this work, we describe a highly innovative gene therapy approach, which is being developed along with the NIH and the FDA. Specifically, our group has developed an allogeneic neural stem cell line that is a carrier for a virus that can selectively infect and break down cancer cells,” explained Dr. Lesniak, the University of Chicago’s director of neurosurgical oncology and neuro-oncology research at the Brain Tumor Center.

The stem cell line used is a neural stem cell line called HB1.F3 NSC. The US Food and Drug Administration has recently approved this cell line for use in a phase I human clinical trial.

Glioblastoma multiforme remains fatal despite intensive treatment with surgery, radiation and chemotherapy. Cancer-killing viruses have been used in clinical trials to treat those tumors that resist treatment with other therapies and infiltrate throughout the brain. Unfortunately, according to Lesniak, this therapy was subject to some “major drawbacks.”

“When you inject a virus into a tumor alone (without a carrier, like NSC), the virus stays at the site of the injection, and does not spread. Moreover, our immune system clears it. By using NSCs, we can achieve a widespread distribution of the virus throughout the tumor mass, since the NSC travel. Also, they act like a stealth fighter, hiding the virus from the immune system.” Lesniak and his co-workers used NSCs loaded with a novel oncolytic adenovirus. This virus selectively targets glioblastoma multiforme in combination with chemo-radiotherapy. Using this strategy, Lesniak’s team was able to overcome the limitations associated with anticancer viral therapies.

Using mice that had glioblastoma multiforme, the research team showed that their neural stem cell line, which is derived from human fetal cells, significantly increased the median survival time of the mice beyond conventional treatments alone. The addition of chemo-radiotherapy further enhanced the benefits of this novel stem cell-based gene therapy approach.

“Our study argues in favor of using stem cells for delivery of oncolytic viruses along with multimodal chemo-radiotherapy for the treatment of patients with glioblastoma multiforme, and this is something that we believe warrants further clinical investigation,” Dr. Lesniak concluded.

Lesniak’s team is completing final FDA-directed studies. He expects to start a human clinical trial, in which a novel oncolytic virus will be delivered via NSCs to patients with newly diagnosed glioblastoma multiforme, early in 2014.

Treatment of glioblastoma multiforme depends on novel therapies,” said Anthony Atala, M.D., Editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. “This study establishes that a combination of conventional and gene therapies may be most effective and suggests a protocol for a future clinical investigation.”

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