Researchers of the Fred Hutchinson Cancer Research Center, in the United States, have discovered a possible way to reduce the toxic side effects that chemotherapy has on the cells of the spinal cord, which consists of modifying the cells with a gene that makes them resistant to chemotherapy.

At the Annual Meeting of the American Society of Gene and Cell Therapy, held last week in Seattle, researchers Hans-Peter Kiem, a member of the Clinical Research Division of the Hutchinson Center; his collaborator Jennifer Adair and Maciej Mrugala, neuro-oncologist of the Seattle Cancer Care Alliance and the University of Washington, have presented data from a clinical trial in which stem cells from the spinal cord of patients with brain tumors were extracted and modified with a retrovirus vector to introduce a gene resistant to chemotherapy. Subsequently, the researchers reintroduced these cells into the patients' body.

In this trial, which was designed to assess the safety and feasibility of this technique, patients safely received blood with genetically modified stem cells that they remained more than a year without apparently causing any harmful effect.

The technique was tested for the first time in patients with a form of terminal brain cancer called glioblastoma. Currently, the average survival of these patients is between 12 and 15 months. The prognosis of patients with glioblastoma is bad, not only because there are no curative treatments, but also because doctors can not effectively use the treatment that exists. Glioblastoma cells make a large amount of a protein called MGMT, which makes them resistant to chemotherapy, so doctors use a second drug - called benzylguanine- to fight MGMT and make the cells of this tumor susceptible to chemotherapy.

However, this powerful 'double hit' is not limited to tumor cells in the brain. Benzylguanine also renders MGMT unusable in normal blood and spinal cord cells, making them also susceptible to the effects of chemotherapy. The effects on the blood and spinal cord of patients can be potentiated and often limit the ability to effectively administer chemotherapy.

"Our first patient is still alive, and without evidence of disease progression, almost two years after his diagnosis"

According to Kiem, "our first results are hopeful because our first patient is still alive and without evidence of disease progression almost two years after his diagnosis."

The results of the study suggest that the administration of modified cells represents a safe method to protect cells in the blood and marrow from the damaging effects of chemotherapy in patients with brain tumors. However, more clinical trials will be needed to determine if this combined with chemotherapy can also improve the survival of patients with glioblastoma.


Bone Marrow Transplant - Mayo Clinic (November 2019).