Wednesday, 7 August 2013

Researchers announce new promising stem cell-based treatment for glioblastoma multiforme

Researchers led by Maciej Lesniak, M.D., have come up with a new type of treatment that pairs neural stem cells with conventional cancer fighting therapies that has shown 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  that appears today in 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, called HB1.F3 NSC, was recently approved by the FDA for use in a phase I human clinical trial.

GBM remains fatal despite intensive treatment with surgery, radiation and chemotherapy. And while cancer-killing viruses have been used in clinical trials to treat therapeutically resistant and infiltrative tumor burdens throughout the brain, “there were major drawbacks,” said Dr. Lesniak.

“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.” By using neural stem cells loaded with a novel oncolytic adenovirus that selectively targets GBM, along with standard of care that includes chemo-radiotherapy, the team was able to overcome these limitations.

Using mice that had GBM, the research team showed how their neural stem cell line, which is derived from human fetal cells, could significantly increase 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 GBM, and this is something that we believe warrants further clinical investigation,” Dr. Lesniak concluded.

The team is completing final FDA-directed studies and expects to start a human clinical trial, in which a novel oncolytic virus will be delivered via NSCs to patients with newly diagnosed GBM, early in 2014.

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

Reference
ALEX L. TOBIAS, a BART THACI, a BRENDA AUFFINGER, a ESTHER RINCĂ“N, a IRINA V. BALYASNIKOVA, a CHUNG KWON KIM, a YU HAN, a LINGJIAO ZHANG, a KAREN S. ABOODY, b ATIQUEU. AHMED, a MACIEJ S. LESNIAK (2013). The Timing of Neural Stem Cell-Based Virotherapy Is Critical for Optimal Therapeutic Efficacy When Applied With Radiation and Chemotherapy for the Treatment of Glioblastoma STEM CELLS : 10.5966/sctm.2013-0039

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