Centrifuges in a gene therapy laboratory. Credit: imageBROKER/Alamy.
Researchers at Bambino Gesù Children’s Hospital in Rome showed that a treatment called Chimeric Antigen Receptor T-cell (CAR-T), already used to treat blood tumours, is also safe and effective against neuroblastoma, the most common solid tumour in children. In a clinical trial enlisting 27 children, the treatment, which involves engineering immune cells so that they attack cancer cells, brought a significant increase in the survival rate.
Neuroblastoma starts from immature nerve cells, and has a global incidence rate between 11 and 13 cases per million children under the age of 15. When treated with surgery, radio or chemotherapy, neuroblastoma patients’ survival rate five years after the diagnosis is above 95%, but if the cancer comes back after treatment, the survival rate falls to less than 10% at three years.
The study authors enrolled 27 children and young adults with relapsed or therapy-resistant neuroblastoma. They collected blood from the patients and isolated their T-lymphocytes, immune cells with the ability to destroy virus-infected or cancer cells. “In our lab, we engineered them, incorporating a segment of DNA designed to produce a specific protein on their surface,” says Concetta Quintarelli, head of the Gene Therapy for Tumours Research Unit at Bambino Gesù Hospital, one of the paper’s authors. “The protein is a receptor binding to GD2, a molecule specifically expressed on the membrane of neuroblastoma cells”.
The modified T-lymphocytes were then infused back to the blood stream, where they multiplied, selectively bound to cancer cells and destroyed them. Nine of the 27 patients had no sign of cancer six weeks after the infusion, 8 had a partial response. Among all treated patients, 11 survived three years after the infusion. Overall, the survival rate after three years was 60%. The results of the clinical trial were published in the New England Journal of Medicine1.
Twenty patients suffered a side effect called cytokine release syndrome, a multi-organ inflammatory reaction due to the release of toxic molecules by the engineered immune cells. It was mild for 19 of them. Only one patient suffered a stronger reaction. The researchers had provided the modified cells with a molecular switch to kill them when needed. This was activated and the side effect was rapidly controlled.
This was its first trial of CAR-T on a solid cancer. “In a few weeks we are starting a CAR-T trial on paediatric brain tumours which express the same GD2 molecular target as neuroblastoma”, says Franco Locatelli, head of the Department of Paediatric Haematology and Oncology at Bambino Gesù Hospital, and senior author of the study. “We are going to arm patients’T-lymphocytes with the same receptor to bind and kill the cancer cells. In the meantime, we are working to improve the design to increase the success rate of treatment for neuroblastoma.”
