Genetically modified immunotherapy and virus to treat glioblastoma

Although therapeutic strategies based on either the use of viruses or immunotherapy have already been tested in patients, the combination of both strategies has never been tested in humans before. Genetically modified viruses and immunotherapy are to be used in patients with glioblastoma, the most aggressive brain tumor.
What is glioblastoma? What is this methodology based on? What is the result of combining both therapeutic strategies?
Glioblastoma, according to the NIH, is a “type of fast growing central nervous system tumor that forms from the glial (supporting) tissue of the brain and spinal cord. Glioblastoma usually occurs in adults and affects the brain more than the spinal cord. Also called grade IV astrocytoma, GBM, and glioblastoma multiforme. ”

For those who are lost: the glia is the set of glial cells, responsible for supporting neurons and controlling their proper functioning. Within the central nervous system (brain and spinal cord) the cells that are part of the glia are oligodendrocytes and astrocytes.

Glioblastoma starts from an astrocyte that undergoes a tumor transformation that induces it to grow uncontrollably, generating a tumor. In children, tumors of the central nervous system represent the second most deadly type of cancer, and in adults, 3.2 cases occur for each inhabitant, being the tumor with the worst survival.

What is immunotherapy?
Immunotherapy is a treatment that consists of stimulating our own immune system to specifically attack cancer cells. Normally, tumors have the ability to block the immune system, preventing antibodies from recognizing cancer cells. The main mission of immunotherapy is to reactivate the immune system’s ability to recognize and attack them again.

These researchers from the University of Navarra Clinic are going to perform immunotherapy using genetically modified viruses. Viruses, remember, have the ability to insert their genetic material into the cells they infect and use the machinery of that cell. In this way, they manage to copy their genetic information to produce many daughter viruses that will continue to infect new cells.

What this new approach is about is taking advantage of this characteristic of viruses to introduce the OX40L gene into tumor cells. This gene is in charge of producing a protein that stimulates the immune system allowing the differentiation of a type of lymphocyte (Th2).

In addition, viruses are genetically modified in two other aspects: the gene responsible for their ability to continue attacking cells after the first infection is removed, making them harmless and will act only where they are injected. In addition, they are modified to specifically bind and infect tumor cells.

What do we achieve by injecting these genetically modified viruses? Perform immunotherapy that stimulates the patient’s immune system. How? The virus only introduces the OX40L gene into glioblastoma cells, so that the tumor cells will express this molecule on its surface, which will allow the immune system to reactivate and attract it to the tumor, increasing the natural immune response against it.

For now? Wait for this new therapeutic approach to the expected results in all patients in which it is applied.

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