Transforming patients’ immune cells so that they target cancerous tumors: this is the principle of cell therapy which has been developing considerably in recent years. We are talking about CAR-T cells. Their effectiveness had already been proven during previous work on leukemia in 2019 in particular.
More recently, it has been demonstrated on cancer cells in the brain. In a new study from Stanford Medical School, scientists gave these CAR-T cells to children with deadly brain and spinal cord tumors. “We have found a treatment capable of shrinking tumors and even improving symptoms,” rejoices Michelle Monje, first author of the study. Their results were published in the prestigious journal Nature.
Deadly childhood cancers
Eleven young patients participated in this study. All suffer from infiltrating brainstem glioma (DIPG) or diffuse midline glioma (DMG), cancers of the brain and spinal cord that mainly strike children and young adults. These rare and particularly aggressive tumors develop in the brain and spinal cord.
As an indication, DIPG, which affects around 50 children per year in France, is one of the most feared pediatric cancers, with an average survival of only 11 months. These cancer cells multiply and invade vital nerve structures. Their diffuse infiltration affects essential functions including motor skills, speech, swallowing and breathing.
“These cancers are extremely difficult to treat due to their location and aggressiveness”deplores to Science and Future Michelle Monje, pediatric neuro-oncologist at Stanford (United States). The study of CAR-T cell therapy, which specifically targets these tumors, therefore represents considerable hope. But how do these improved cells work?
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CAR-T lymphocytes, these immune super cells
This method is based on immune cells naturally present in our body: T lymphocytes. These are key cells of the immune system, capable of recognizing and destroying infected cells. But because cancer cells come from our own cells, they sometimes slip through their nets.
To overcome this gap, scientists discovered a revolutionary method in the 1990s: modifying T lymphocytes so that they specifically target certain cells. These modified lymphocytes are called CAR-T cells. The principle is as follows: researchers take T lymphocytes from patients and modify them so that they identify a distinctive sign of cancer cells. Once this skill is acquired, the lymphocytes are introduced into the patients’ bodies and can attack cancer cells. Here the distinctive sign is GD2, a small molecule present on the surface of cancer cells, a target of choice for CAR-T cells, because it is widely expressed.
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Reduce the size of the tumor until it disappears?
Of the participants, nine showed considerable benefits. Their neurological functions have been improved: “DIPG and gliomas infiltrate and integrate at the synapses of neurons”, indicates the author. “Nervous system activity is actually the driving force behind cancer growth.” Gliomas therefore cause dysfunction of neuronal circuits, but do not generally destroy them.
“In this trial, we found that when CAR-T cell therapy eliminated cancer cells, neurological functions recovered quickly,” she adds. For four patients, the tumor shrank by more than half and for one of them, it even disappeared completely on brain scans. Researchers are hopeful that he will be cured.
Although the treatment is promising, it is cumbersome and has significant side effects. Before receiving the CAR-T cells, participants underwent chemotherapy to prevent their immune systems from attacking the modified cells. The researchers first administered the lymphocytes intravenously. But several side effects then occurred: fever, low blood pressure, as well as temporary neurological effects due to inflammation within the tumor.
Patients who showed benefits from the first injection then received two additional injections, directly into the cerebrospinal fluid. This time, patients faced fewer side effects. They were able to receive other regular injections.
“The results obtained in this cohort are very encouraging. However, we still have much to do to achieve complete and lasting answers for all patients. says Michelle Monje. Today, their work aims to understand the disparities in the results of this treatment: why have some patients not benefited from it? “The study of biological differences that could explain these disparities in therapeutic response has generated hypotheses that we are currently testing in the laboratory, with the aim of optimizing this therapy in the future. she concludes.
