Encapsulated stem cells (green) track and destroy GBM tumor cells (red). Credit: Shah lab (CSTI)

Glioblastomas (GBM) are very aggressive cancers of the brain and spinal cord. Brain cancer, like GBM, is difficult to treat because many therapeutics for cancer cannot cross the blood-brain barrier, and more than 90 percent of GBM tumors return after surgical removal despite surgery and subsequent chemo- and radiation therapy are the most successful treatments. treat the disease. In a new study led by researchers from Brigham and Women’s Hospital and Harvard Medical School, researchers developed a new therapeutic strategy to treat GBM after surgery using stem cells taken from healthy donors designed to attack GBM-specific tumor cells. This strategy demonstrated great efficacy in preclinical GBM models when 100 percent of mice lived more than 90 days after treatment. The results are published in The nature of communication.

“This is the first, as far as we know, study that identifies target receptors tumor cells before starting therapy and using biodegradable, gel-encapsulated, stem cell-based stem cell therapies after GBM surgery, ”said Khalid Shah, MS, MD, Director of the Stem Cell Center and Translational Immunotherapy (CSTI) and Deputy Brigham Neurosurgery Department and professors at Harvard Medical School and the Harvard Stem Cell Institute (HSCI). from the finished tank “.

Many cell-based cancer treatments have been developed by the patients themselves stem cells or immune cells. However, with a disease like GBM, most patients undergo surgery in the first week after diagnosis due to the rapid progression of the disease, giving little time to develop therapeutic agents from their own cell types. Instead, scientists have developed a new approach to the use of allogeneic stem cells or cells from healthy people so that the drug is readily available for administration immediately during surgery. Shah and his colleagues evaluated the effectiveness of several capsules that carry therapeutic stem cells in the brain, and found that the biodegradable hydrogel capsule successfully transports treatment without flushing. cerebrospinal fluid.

Researchers have for the first time discovered special receptors invented by “death receptors” on circulating tumor cells (CTC) – or cancer cells into the bloodstream – by a genetic biomarker commonly expressed on tumor cells. Once identified, they took stem cells from the bone marrow of healthy human donors and developed cells to release a protein that binds to death receptors and initiates cell death. They also built a protective switch into the stem cell system, which allows you to track stem cells with PET imaging and, when activated, destroys stem cells and further enhances cancer cell death. Finally, the Shah team evaluated the efficacy of therapeutic bifunctional cells (MSCs)Bif) in animal models of primary and recurrent GBM tumors after surgery.

Notably, all mice that received the gel-encapsulated stem cell therapy were still alive 90 days after treatment, compared with mice that underwent surgery alone, with a median survival of 55 days. The researchers further evaluated the safety of this clinical treatment by conducting several studies using different doses of MSC therapy in mice. They showed no signs of toxicity among mice with or without tumors.

The results of the study pave the way for clinical trials in phase I clinical trials in patients with GBM who undergo brain surgery for the next two years. Shah and his colleagues note that this therapeutic strategy will be applicable to a wider range of solid tumors and that further research into its application is warranted.

“In addition, this therapy is significantly exposed academic performanceThese findings suggest that we can use healthy people’s stem cells to treat cancer patients, ”Shah said. cells and immune cells y tumor a microenvironment that we will one day be able to use to treat a wide range of difficult-to-treat cancers such as GBM ”.

Designed stem cells that are on sale target breast cancer that metastasizes to the brain

Additional information:
Identification of target receptors and subsequent treatment of resected brain tumors using encapsulated and engineered allogeneic stem cells, The nature of communication (2022). DOI: 10.1038 / s41467-022-30558-3

Citation: Scientists Develop Stem Cells for the Treatment of Aggressive Brain Cancer (2022, May 19), Retrieved May 19, 2022, from https://medicalxpress.com/news/2022-05-scientists-shelf-stem-cells-aggressive .html

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