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Last year, the Nobel Prize in Medicine was awarded a revolutionary new way to trigger the immune system's response to attack cancer cells. The promise of immunotherapy is extraordinary and marks a major turning point in the fight against cancer as it prevents cancer cells from blocking the immune system's response.
This week, a team from Vanderbilt University announced that she had found another way to engage the immune system in a battle against malignant cancer cells by reactivating the T cells that the cancer cells had already closed.
Cancer: a cunning enemy
Cancer cells are insidious for many reasons, but one of the most daunting features of cancer is its ability to hide, shut down or thwart the immune response of the body responsible for treating infections and other malignancies in the body. the body.
One way to do this is to invade the T cell itself with tumor cells. As a result, the immune system's response ignores the tumor cells it is supposed to fight. The technique that won the Nobel Prize, called Checkpoint Blockade, is intended to prevent this infiltration, allowing the immune system to do what it was always supposed to do: kill cancer cells.
"The tumors are rather connotated and have evolved in many ways to avoid the detection of our immune system," said John T. Wilson, an badistant professor in chemical engineering and biomolecular and biomedical engineering at Vanderbilt. "Our goal is to rearm the immune system with the tools it needs to destroy the cancer cells. "
Free T cells
In an article titled "Endosomolytic Polymersomes Increase the Activity of Cyclic Dinucleotide Agonists STING to Enhance Cancer Immunotherapy" in the Journal Nature Nanotechnology, The Vanderbilt team showed that it was possible to reactivate the T cells that had been closed by the tumors that they were fighting.
They did this by targeting the T cells that the tumors had already infiltrated and disarmed. To do this, they designed a particle at the nanoscale that could induce disabled T cells to fight back, thus reviving the immune response short-circuited after its activation by cancer.
"The blocking of checkpoints has been a major breakthrough," Wilson said, "but despite the considerable impact it continues to have, we also know that many patients do not respond to these treatments. We have developed a nanoparticle to detect tumors and deliver a specific type of molecule naturally produced by our body to fight cancer. "
This molecule, cGAMP, is crucial in that it acts as a switch for what is known as the interferon gene stimulator pathway (STING). STING is a mechanism used by the body to trigger a response to an infection or a group of malignant cells. For the most part, cGAMP is the general of the horse who shouts "charge!" To an army of T cells ready to fight the threats that weigh on the body.
Successful tests encourage further study
The team developed the nanoparticle that administered cGAMP to infiltrate cells from "smart polymers" that respond to changes in pH. Daniel Shae, Ph.D. The Wilson team candidate designed the nanoparticle to improve the power of the cGAMP contained inside and, after nearly two dozen refinements, the nanoparticle that she built actually activated STING in the T cells of the mice, then in the tumors themselves carried by the mouse. finally in samples of cancerous human tissue.
The human tissue test is limited to melanoma, but according to Wilson, the technique should be just as effective against other forms of cancer.
"It's really exciting," Shae added, "as it demonstrates that someday this technology could be successful in patients."
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