CAR-T therapy [1] helped reduce brain tumors in young patients [2] and restored their neurological function. For one of the participants in this clinical trial conducted by Stanford Medicinetherapy made it possible to erase “ all detectable traces » of brain cancer from which he suffered, a cancer generally considered incurable. Two of them saw their symptoms decrease without the overall volume of the tumor changing. These results were published in the journal Nature [3].
A first patient cured?
Of the 11 participants who received CAR-T therapy in the trial, nine showed benefits [4]. Four saw the volume of their tumor reduced by more than half. And one of these four participants, Drew, aged 20, obtained a “ full answer »: his tumor[5] has disappeared from brain scans. Although it is too early to tell if he is cured, he is in good health four years after diagnosis.
Drew was diagnosed with DIPG in November 2020, during his junior year of high school. He had sought medical attention because of unusual headaches, strange movements in his left eye and partial paralysis on the left side of his face. A few hundred children or young adults receive such a diagnosis in the United States each year, their median survival time is approximately one year. [6]. Radiotherapy only provides temporary relief and there is no effective chemotherapy treatment. Because their malignant cells mix with healthy cells, tumors cannot be surgically removed.
CAR-T cells have been approved by the Food and Drug Administration since 2017 to treat blood cancers, their benefit remains to be demonstrated against solid tumors (see CAR-T cells and leukemia: encouraging long-term results).
Prospects for improving treatment
As this was the first-in-human trial of CAR-T cells for DIPG, the study primarily aimed to assess the feasibility of the treatment and monitor side effects. By analyzing the decrease in tumor size in trial participants, researchers believe that “ Drew’s excellent answer is not a fluke » and that future patients could derive similar benefits.
The team is currently investigating ways to improve the therapy, for example by suppressing aspects of the immune response to CAR-T cells that could “favor” the tumor.
« We have already formulated some hypotheses on how to improve outcomes, both for this therapy and more generally for immunotherapy of central nervous system cancers “, says the lead author of the trial, Michelle Monje, professor of neurology at Stanford Medicine. « Although this trial represents progress, we still have work to do to reduce the toxicity of the treatment and improve the benefits for patients. », Specifies Dr Crystal Mackall, also co-author of the study.
[1] « The objective is to produce, using a gene introduced into their nucleus, “chimeric antigen receptors” (CAR) on the surface of T lymphocytes. Thanks to this receptor, CAR-T cells are capable of recognizing tumor cells and attach to them. Genetic modification also makes it possible to introduce a “costimulation” element which allows the CAR-T cell to activate and attack the cancer cell once attached to it. » (Source: Gustave Roussy, CAR-T cells)
[2] The median age of participants was 15 years old, and their tumors had been diagnosed an average of five months before they entered the trial.
[3] Michelle Monje et al, Intravenous and intracranial GD2-CAR T cells for H3K27M+ diffuse midline gliomas, Nature (2024). DOI: 10.1038/s41586-024-08171-9.
[4] a reduction in the volume of their tumor, an improvement in their function on neurological examination, or both
[5] He had diffuse intrinsic pontine glioma, or DIPG.
[6] Study participants lived an average of 20.6 months after diagnosis, with two living more than 30 months.
Source : Medical Xpress, Stanford University Medical Center (13/11/2024)
