Researchers have developed a novel therapeutic strategy for treating brain tumours using stem cells taken from healthy donors engineered to attack specific tumour cells. Published in Nature Communications, the new study describes allogenic “off-the-shelf” clinical-grade bifunctional mesenchymal stem cells (MSC) and a safety kill switch to treat glioblastoma (GBM).
Local delivery of cell-based therapies presents a promising potential for the treatment of GBM as it sidesteps the critical concerns of the brain-blood barrier and allows for therapeutic agents to reach the desired concentration at the target area.
Fighting brain tumours
After decades of advances in treatment strategies for different cancer types, highly fatal brain tumours, GBM still present a challenge for treatment.
Typically, surgery followed by radio or chemotherapy is the standard of care for GMB patients. Unfortunately, 90% of these tumours recur and, according to the Cancer Genome Atlas, there is a 6% 5-year survival rate.
Many cell-based therapies for cancer are taken from a patient’s own stem cells. However, in a disease like GBM, most patients undergo surgery in the first week after receiving their diagnosis due to the disease’s rapid advancement. This allows little time to develop therapeutics from their own cell types.
Considering the crucial and incredibly limited timeline from diagnosis to primary surgical intervention in GBM patients, “off-the-shelf” engineered stem cells offer a promising therapeutic strategy to target lingering GBM post-surgery. Using cells from healthy individuals could offer an option where the remedy is easily available to administer immediately at the time of surgery.
Identifying brain tumours
Circulating tumour cells (CTC) normally constitute one cancer cell per billion normal blood cells and present an important tool for cancer diagnosis. However, CTC detection strategies typically rely on targeting a molecule (EpCAM), which is not present on GBM cells.
Captured from the blood of mice bearing GBM and patients diagnosed with GBM, the new study identified special receptors coined “death receptors”. Once identified, the tumour cells could be targeted.
The authors say, “We demonstrate the successful use of a CTC technology approach to the detection of cell surface target molecules that has the potential to be translated into clinical applications to select patients appropriate for the targeted therapy.”
Treating brain tumours safely
Using stem cells from healthy adult human donors, the researchers were able to engineer the cells to release a protein that binds to the death receptors and initiate cell death.
The team evaluated the efficacy of several capsules that carry the stem-cell therapeutic in the brain and found a biodegradable hydrogel capsule to successfully transport the treatment without being washed away by cerebrospinal fluid.
They also designed a kill-switch which, when activated contributed to an additional killing of the tumour cells. Kill switches provide a unique way to safeguard therapeutics and add an additional layer of safety that can be controlled for biological therapies. Given that safety is paramount in clinical translation, it is essential to enhance the safety of the therapeutic.
In the study, all mice that received the gel encapsulated stem cell-based therapeutic after surgery were still alive 90 days post-treatment. Mice that solely underwent surgery had a mean survival time of 55 days. No signs of toxicity were found among mice with or without tumours.
The authors stated, “Allogeneic cells can be fully characterised and banked, and therefore allow for the development of “off-the-shelf” therapeutics for various clinical conditions, including brain tumours.”
Written by Poppy Jayne Morgan, Front Line Genomics
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