Caring for a woman who suffered a brain tumor as a child: the success of CAR-T immunotherapy

BarcelonaA woman who was diagnosed with neuroblastoma, a brain cancer, as a child has been tumor-free for 18 years thanks to treatmentCAR-T cell immunotherapyThe case is covered in a study published in the journal Nature Medicine and it is assumed that the woman is the patient with this type of cancer who has lived the longest without the presence of the tumor until now, which makes the researchers think that she has been completely cured.

In the same study – a review of a small clinical trial carried out between 2004 and 2009 by researchers at the Baylor College of Medicine (Houston, USA) with 19 children with neuroblastoma, a tumor of the nerve cells that can have a very poor prognosis – in which follow-up was stopped.

"As these patients had active neuroblastoma when they were treated" and in the time in which the American researchers followed them they had not relapsed, "they could [also] be cured," the authors of the work carefully state.

Neuroblastoma, which affects nerve cells, is one of the most common tumors in children under five years of age. Treating it is challenging: surgery is often used, combined with chemotherapy and radiotherapy, which carry a significant risk that patients who survive will end up developing a new tumor as a side effect, among other harmful impacts that diminish their quality of life.

In this study, researcher Helen Heslop led a phase 1 clinical trial with CAR-T cells, (the acronym in English forchimeric antigen receptor-T), a treatment in which T cells – a type of white blood cell of the immune system – are obtained from the patient himself, genetically reprogrammed in the laboratory to specifically recognize and eliminate tumor cells, and then given back to the patient. In this trial, they tested T cells engineered to recognize GD2, a protein that is highly expressed in neuroblastoma.

The phase 1 clinical trial aimed to determine whether CAR-T treatment was safe for pediatric patients with neuroblastoma and proved that it was. However, of the 19 patients, 12 died between 2 months and 7 years after receiving the treatment, due to disease relapses. Of the remaining 7 patients, five continued to be followed up 8 to 15 years later and were at that time free of neuroblastoma.

One of the patients who responded to immunotherapy is the woman who is in complete remission 18 years later. At the time of receiving it, she also had lesions in her bones and with only one Administration of modified T cells achieved complete remission"He first received standard therapy with surgery and chemotherapy, and when we gave him CAR-T he still had disease," says Heslop, who acknowledges that "we don't know why he did so well" compared to the other trial participants. "Maybe the tumor was more susceptible or he had less disease than other patients in the trial," he speculates.

The basis for attacking solid tumors

In the Heslop trial, they also used a second type of lymphocytes that responded to the Epstein-Barr virus, since it is estimated that 90% of the population are carriers. "We used specific T lymphocytes against the Epstein-Barr virus in the hope that they would last longer in the body, since they would be stimulated by the viral reactivation that occurs in all people who have infection with this virus," explains the researcher in an email to the ARA.

These encouraging results are added to those obtained in 2023 by a group of Italian researchers from the Niño Jesús Pediatric Hospital and published in New England Journal of Medicine, where they also used modified T cells to treat high-risk neuroblastomas in 19 patients between 1 and 25 years of age, of whom 17 responded to the treatment.

Both studies pave the way for progress towards the application of this type of therapy in solid tumors as well. Until now in Spain this type of treatment has only been tested to treat leukemia, although there are studies underway to evaluate its efficacy against breast cancer and other blood tumors, such as multiple myeloma,lymphomaseitherlupusBoth studies provide valuable information on the long-term effects of treatment with these immunotherapies on the quality of life of survivors.

The patient, who has been tumour-free for 18 years, has been the mother of two healthy children and has not suffered any unwanted side effects from the treatment. For Marta Alonso, an expert in paediatric tumours and researcher in the Solid Tumour Programme at CIMA and the Clínica Universidad de Navarra, this is precisely the value of this study: "It shows us how the patients are 15 years later." In statements to ARA, this researcher emphasises that, in addition to advancing the development of increasingly effective therapies, "it is essential to have long-term studies that provide us with knowledge about the quality of life of survivors." The issue is that in other types of tumours, the administration of second and especially third generation T cells has been seen to cause brain inflammation and neurodegenerative disease and secondary tumours in some patients.