A man from the United States suffering from the most aggressive type of brain tumor, a glioblastoma, is the first patient in the world in whom an experimental immune therapy has been successfully tested, opening a path of hope for the treatment of this type of cancer.
Immunotherapy, based on CAR-T cells, was administered after chemotherapy and radiotherapy had failed to slow the progression of the cancer and when the patient had no other treatment options left. Two days after receiving the immune cells, which were inoculated in a single infusion directly into the brain, the size of the tumor had shrunk by 18.5%. Ten weeks later, the reduction was already 61%.
“The patient's response continued to improve and was maintained in his last evaluation, more than 150 days after the infusion,” reports the medical and scientific team that developed the therapy in The New England Journal of Medicine, where they presented the case yesterday.
Two other patients who received the same therapy also had rapid regression of their tumors from the first day after receiving the CAR-T cells. But in these two cases the effectiveness of the treatment was short-lived and the cancer soon progressed again.
The researchers, from Massachusetts General Hospital and Harvard University, attribute the loss of efficacy in these two patients to the disappearance of CAR-T cells from the brain. This, in turn, is attributed to the use of low doses of CAR-T cells because it was the first time the treatment was tested in people. Once it has been proven that the side effects are tolerable, in the future it is expected to increase the effectiveness with higher doses.
“The fact that tumor reductions have been achieved in the first three patients treated is very promising,” says Sònia Guedán, head of the cellular immunotherapies group for cancer at the Idibaps institute in Barcelona. “These results tell us that we are going in the right direction, although there are still things to improve.”
“It is progress, but it is not yet ready to reach patients,” says María Vieito, a glioblastoma specialist at the Vall d’Hebron Institute of Oncology (VHIO), along the same lines.
CAR-T therapies involve extracting immune cells from patients' blood; modify them in the laboratory so that they recognize cancer cells; multiply them; and inoculated again into patients to attack the cancer. They are already used successfully for the treatment of hematological cancers such as some lymphomas and leukemias, but there are still no CAR-T therapies approved for solid tumors.
Glioblastoma, being a type of tumor with a poor prognosis and whose treatment has barely improved in the last fifteen years, is one of the cancers where the potential of CAR-T cells is being investigated the most.
The three patients treated at Massachusetts General Hospital received CAR-T cells modified to recognize a protein that is found in 30% of glioblastomas and that is not found in healthy cells (specifically, variant III of the EGFR protein). In addition, they are modified to encourage the immune system to attack the original EGFR protein, which is found in 80% of glioblastomas. They are the first three participants in a clinical trial in which it is planned to enroll 21 patients and which will conclude in June 2026.
Other research groups are developing other CAR-T cell therapies against glioblastomas based on different proteins, although it is not yet known which of them will be the best.
