Scientists develop ‘standard’ stem cells designed to treat aggressive brain cancer

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May 19, 2022

(News from Nanowerk) Glioblastomas (GBMs) are very aggressive cancerous tumors of the brain and spinal cord. Brain cancers like GBM are difficult to treat because many cancer treatments cannot cross the blood-brain barrier, and more than 90% of GBM tumors come back after being surgically removed, although surgery and chemo and Subsequent radiation therapy is the most effective way to treat the disease.

In a new study (Nature Communication, “Identification of target receptors and subsequent treatment of resected brain tumors with encapsulated and modified allogeneic stem cells”) led by researchers from Brigham and Women’s Hospital and Harvard Medical School, scientists have developed a new therapeutic strategy to treat GBM after surgery using stem cells taken from healthy donors designed to attack tumor cells specific to GBMs. This strategy has demonstrated profound efficacy in preclinical models of GBM, with 100% of mice living more than 90 days after treatment. Encapsulated stem cells Encapsulated stem cells (green) stalking and killing GBM tumor cells (red). (Image: Shah lab, CSTI)

“This is the first study to our knowledge that identifies target receptors on tumor cells before initiating treatment and uses biodegradable, gel-encapsulated, ready-to-use stem cell therapy after a GBM tumor surgery,” said Khalid Shah. , MS, PhD, Director of the Center for Stem Cell and Translational Immunotherapy (CSTI) and Vice Chair for Research in the Department of Neurosurgery at Brigham and faculty at Harvard Medical School and the Harvard Stem Cell Institute (HSCI). “In the future, we will apply this strategy to rapidly identify target receptors after being diagnosed with GBM, and then deliver ready-to-use, gel-encapsulated stem cell therapy designed from a prefabricated tank.

Many cell therapies for cancer are derived from the patient’s own stem cells or immune cells. However, in a disease like GBM, most patients undergo surgery within the first week of being diagnosed due to rapid disease progression, leaving little time to develop therapies from of their own cell types. Instead, scientists have developed a new approach to use allogeneic stem cells, or cells from healthy individuals, so that the remedy is readily available to be administered immediately at the time of surgery.

Shah and his colleagues evaluated the effectiveness of several capsules that transport stem cell therapy into the brain and found a biodegradable hydrogel capsule to successfully transport the treatment without being washed away by cerebrospinal fluid.

The researchers first identified special receptors called ‘death receptors’ on circulating tumor cells (CTCs) – or cancer cells in the blood – using a genetic biomarker commonly expressed on tumor cells. Once identified, they took stem cells from the bone marrow of healthy human donors and engineered the cells to release a protein that binds to death receptors and initiates cell death.

They also incorporated a safety switch into the stem cell system that tracks stem cells through PET imaging and, when activated, eradicates stem cells and further enhances cancer cell death. Finally, Shah’s team evaluated the efficacy of therapeutic bifunctional cells (MSCBif) in animal models of primary and recurrent GBM tumors after surgery.

Notably, all mice that received the encapsulated stem cell therapeutic gel after surgery were still alive 90 days after treatment, compared to mice that only underwent surgery, which exhibited life span. average survival of 55 days.

The investigators also assessed the safety of this clinical treatment by conducting several studies using different doses of the MSC therapy on mice. They found no signs of toxicity in mice with or without tumors.

The study results pave the way for Phase I clinical trials in GBM patients undergoing brain surgery within the next two years. Shah and colleagues note that this therapeutic strategy will be applicable to a wider range of solid tumors and that further investigation into its applications is warranted.

“Beyond the significant success rate of this therapy, these results suggest that we can use stem cells from healthy individuals to treat cancer patients,” Shah said. “This work lays the groundwork to start building a therapeutic stem cell biobank targeting different receptors on tumor cells and immune cells in the tumor microenvironment that we can one day use to treat a wide range of difficult-to-treat diseases. cancers like GBM.



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