Compilation
Immune cell therapy has reduced brain tumors in children. restore your neurological functions and in the case of a patient who took part in a clinical trial conducted at Stanford Medicine (USA), he was able to completely eliminate detectable traces of a type of brain cancer previously considered incurable, according to a study published in the journal Nature. This essay notes one of the first successes in the fight against solid tumors The use of modified immune cells known as CAR-T cells offers new prospects for children suffering from a group of deadly brain and spinal cord tumors, including a cancer called diffuse intrinsic pontine glioma or DIPG.
The results of the study were published on November 13 in the specified scientific journal. In October US Food and Drug Administration (FDA) has granted this CAR-T therapy “advanced regenerative therapy“, which gives researchers access to an expedited version of the Food and Drug Administration (FDA) approval process.
Belonging 11 participants who received CAR-T cells in the study, nine showed benefits. Nine patients experienced functional improvement in the disability caused by their disease. In four people, the volume of tumors was reduced by more than half. And one of these four participants had a complete answer.This means his tumor disappeared in a brain scan. Although it is too early to say whether he has recovered, He is healthy four years after diagnosis.
“This is a fatal disease for which we have found a CAR-T therapy that can produce significant tumor regression and clinical improvement.”“warns Dr. Michel Monge, The study’s lead author, Milan Gambhir, is a professor of pediatric neuro-oncology and a professor of neurology at Stanford University School of Medicine. “While there is still a long way to go to figure out how to optimize this for each patient, it is very exciting that the patient had a complete response. I hope it’s cured.”
Diffuse midline gliomas, which can grow in the brain or spinal cord, have Average survival rate is about a year. Radiation therapy provides only temporary relief, and there are no effective chemotherapy drugs. Because their malignant cells mix with healthy cells in key neurological structures, the tumors cannot be removed surgically. DIPG, disease subtype occurring in the brain stem, has five-year survival rate less than 1%.
In this grim scenario, the research team didn’t know what to expect from CAR-T cells, although preclinical studies in rodents were promising. CAR-T cells, or chimeric antigen receptor T cells, are created by removing some of a patient’s own T cells and modifying them to bind to a specific molecular target. The cells are returned to the patient’s body, where trigger an immune response against cancer cells that have a molecular target.
In a new study “one of the biggest surprises was the huge clinical effect we saw“, emphasizes the main author of the study, Dr. Crystal McCallprofessor at the Ernest and Amelia Gallo School of Medicine and professor of pediatrics and medicine. As tumors progress, they cause profound disability. Patients may lose the ability to walk, smile, swallow, hear, and speak. They can experience neuropathic pain Spinal cord injury often results in severe, stabbing or burning pain, as well as paralysis, loss of sensation and urinary incontinence.
Before the trial, McCall said, researchers weren’t sure whether shrinking the tumors would eliminate the horrific symptoms. But then: ““we could see clear evidence of reversibility”.
According to Ignacio MeleroProfessor of Immunology at the University of Navarra, Researcher at the Center for Applied Medical Research (CIMA) and Co-Director of the Department of Immunology and Immunotherapy at the University Hospital of Navarra, “The most interesting thing about the study is that intracavitary locoregional administration is the way to go. “By using this intracavitary or intratumoral route of administration, the efficacy of CAR-T cells against solid tumors can be optimized for maximum impact.”He stated this according to testimony collected Scientific media center.
The type of CAR-T therapy used in the study was developed at Stanford Medical University. Thanks to this, the researchers were able to demonstrated that CAR-T cells targeting GD2 eradicate DIPG tumors in animal models.
The new study reports on the first 13 patients enrolled in an ongoing study that may include those with DIPG or diffuse midline glioma of the spinal cord. the average age of the participants was 15 years and their tumors were diagnosed on average five months before they joined the court. Ten had DIPG, three had diffuse midline glioma of the spinal cord.
Since this was the first human trial of CAR-T cells for DIPG, the researchers first wanted to see if they can create cells for every person, Determine a safe dose of cells and monitor for side effects. Their secondary goal was to begin evaluating clinical benefits.
Before receiving CAR-T cells, participants received chemotherapy to prevent their immune system from attacking the modified cells. They received the first dose of CAR-T cells intravenously and were monitored by researchers for immunological and neurological side effects.
After receiving the cells intravenously, all participants suffered to some degree from cytokine release syndrome, also known as “cytokine storm”with symptoms such as fever and low blood pressure, as well as temporary neurological side effects due to inflammation within the tumor. The team tested two doses of CAR-T cells and found that the lower dose was safer because it provoked Less serious side effects of cytokine storm.
Of the 11 participants who received CAR-T cells, nine experienced benefits: reduced tumor volume, improved function on neurological examination, or both. These nine participants received additional doses of CAR-T cells
injected into the cerebrospinal fluid of their brain.Injecting the cells directly into the cerebrospinal fluid caused fewer side effects. Participants continued to receive the brain cell infusion every one to three months for as long as it provided benefit. Overall, participants experienced less inflammation with subsequent cell infusions. The researchers said that in the next arms of the study they will test injecting the cells into the cerebrospinal fluid from the beginning.
Majority of nine participants who benefited from CAR-T cells there was an improvement neurological symptoms and reduction in tumor size. However, two of them experienced a decrease in symptoms without a change in overall tumor volume. As their tumors shrank, several participants They regained their lost abilitiesfor example, when walking, or there was a change in symptoms such as incontinence, paralysis or neuropathic pain. Among the four people with the best answers tumor volumes decreased by 52%, 54%, 91% and 100%. Study Participants they lived an average of 20.6 months after diagnosis.; two of them lived more than 30 months and one was still alive four years after being diagnosed with DIPG.
“The results represent a true ‘end of approval’ for this immunotherapy in terms of safety and efficacy, as they document a case of complete remission in a patient with diffuse midline glioma, which is an incurable disease. This study, along with others previously published, demonstrates that this type of adoptive cell immunotherapy will become the standard treatment for brain tumors in the short term and paves the way for future evolution of this type of therapy to improve their effectiveness.”emphasized Dr. Luis Alvarez-VallinaHead of the Department of Collaborative Cancer Immunotherapy at the Hospital 12 October-CNIO.
Researchers analyzed the maximum size reduction tumors of all participants and found that responses followed a normal distribution or bell curve, suggesting that the excellent response of the surviving patient was not a coincidence and that future patients may experience similar benefits. The research team is currently studying how the therapy can be improved, for example by suppressing aspects of the immune response to CAR-T cells that may contribute to tumor development.
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