Engineered cell therapy for cancer gets thumbs up from FDA advisers

FDA green lights engineered cell therapy for cancer treatment.

In an exciting development in the battle to cure cancer, an FDA panel this month unanimously recommended the approval of CTL019 (tisagenlecleucel), a receptor in CAR-T therapy to be used in the treatment of young patients with lymphoblastic leukemia.

The Oncologic Drugs Advisory Committee (ODAC) voted 10 to zero in favour of the therapy, which will genetically manipulate the patient’s immune cells to destroy cancers within the body. While the FDA is under no legal obligation to follow recommendations from such panels, it is the norm for them to do so, meaning the global oncological community could soon have another treatment at it’s disposal in a bid to combat cancer.  

What is CAR-T?

CAR-T therapy stands for chimeric antigen receptor T-cell therapy, an exciting and thought-to-be effective immunotherapy treatment.

The CAR-T cells are essentially genetically reengineered immune cells that are “trained” to isolate and kill cancer cells within the body. The drug in question, tisagenlecleucel, is manufactured by Novartis and was recommended for use in CAR-T by the panel on July 12th. Novartis hopes to use the drug to treat children and adolescents battling Acute lymphocytic leukemia (ALL), specifically B-cell lymphoblastic leukaemia.

The treatment is created in individual batches in accordance with each patient’s blood, a process that takes Novartis about 22 days to complete. A single batch of tisagenlecleucel is created by taking a sample of white blood cells from a patient, which are then purified and sent to a central processing centre. Here, the T cells are injected with the chimeric antigen receptor, programming them to “recognize” leukemia cells. The CAR-T cells will be grown in a culture prior to being re-introduced into the patient.   

In the United States, research has shown that roughly 15 per cent of those young patients affected with the disease will  relapse, but studies have shown that CAR-T therapies can lead to lasting remission. In one trial of tisagenlecleucel, 82.5 per cent of participants experienced overall remission.  

Is CAR-T safe?

The use of CAR-T is still in it’s infancy, and while the panel recently voted that the pros outweighed any cons, some scientists have raised concerns about the risks involved.   

For example, in the aforementioned tisagenlecleucel trial, nearly half of the patients involved experienced an extreme inflammatory reaction. Cytokine release syndrome is a common reaction to antibody infusions, and 47 per cent of participants experienced this reaction, the symptoms of which can include high fevers and - in serious cases - organ failure. Though a substantial number of patients were affected, trial clinicians were able to successfully manage this reaction, along with other short-term neurological issues including seizures and hallucinations. Previous CAR-T trials have been blighted by more serious neurological problems such as swelling of the brain, which have in some cases resulted in patient death. However, the  CAR-T therapy used by Novartis in this most recent trials differ to that of the cells in previous trials, and notably the patients who experienced fatal consequences took part in adult trials as opposed to these, which was exclusively trialled on children and young adults.

In summary:

While it still may be early days for CAR-T therapy, the panel was overall quick to praise this most recent development. This can be seen looking at the comments from panel member Malcolm Smith, paediatric oncologist at the US National Institutes of Health: “This is a major advance, and is ushering in a new era,” he said.