A living drug – FDA approves gene altering cancer treatment

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Immunotherapy is an exciting field of research. It investigates different approaches to harness the immune systems ability to recognise and destroy mutated cells. Different ways have been utilised to enhance the immune systems response to cancer. One way is to modify genes in immune cells harvested from the patient, and reinfusing them back into the person to fight the cancer. Some call the cells living drugs as the modified cells can actively seek out cancer cells, destroying them.

The FDA now approved such an approach to treat leukaemia, marking the first time a gene therapy product has been approved as disease treatment.

The now approved chimeric antigen receptor (CAR)-T cell therapy is called Kymriah (tisagenlecleucel or CTL019) and produced by Novartis. In this personalised medicine, T cells are genetically modified to express antigen receptors that recognise the tumour antigen CD19. Reinfused T cells proliferate and kill leukaemia cells expressing CD19 on their surface.

The treatment plan gained approval following a multicenter (25 sites in 11 countries) clinical trial of 63 paediatric and young adult patients with relapsed or refractory B cell precursor acute lymphoblastic leukaemia (ALL) showed a remission rate of 83% within three months.

While this is exciting news for patients and the therapy approach can technically be expanded to many tumour types as long as they express a tumour antigen, the side effects limit the use of the therapy at the moment. Exponential proliferation and activation of the modified CAR T cells can cause high fevers and flu-like symptoms – called cytokine release syndrome (CRS), and neurological problems, including seizures and delirium which can be life-threatening. CRS affected 47% of patients treated with Kymriah during the trial – however all patients survived.

Weighing side effects against the positive anti-cancer effects of the gene therapy, the FDA decided to approve it for treatment of paediatric and young adult patients (aged 3-25) suffering from B cell ALL. But only in so far untreatable cases. Cases in which the cancer has not responded or returned after initial conventional treatment. This accounts for 15-20 percent of patients – approximately 600 people in the USA per year. While this approach uses an easily accessible source of T cells, the large effort needed to modify the cells makes it expensive – $475,000.

Aiming to make the therapy as safe as possible, Novartis is limiting the therapy to 30-35 medical centres where medical personnel had extensive training with the treatment and  is equipped to handle CRS. So hopefully side-effects will be managed well. However, only if the approach becomes less toxic can it be considered for the treatment of more patients.


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