Through the cellular modification of your own blood, a notorious cancer can be treated
Writer: Anisa Mohamed
Editor: Bhavika Hotchandani
Cancer, the world’s greatest medical challenge, is one of the leading causes of human deaths worldwide, accounting for 9.6 million deaths in 2018 according to World Health Organisation. We question whether the billions of funds going towards its research is fruitless. We build conspiracy theories on whether pharmaceutical companies have already developed cures for the hundreds of different cancer types. We are sitting ducks waiting for news outlets to report on the latest updates, be it the successes or failures of novel chemotherapy. Nevertheless, the wait for a promising treatment for Acute Lymphoblastic Leukaemia (ALL) has ended, thanks to a leading multinational pharmaceutical company – Novartis. Novartis has made an early commitment to the emerging field of immuno-oncology with one of its facilities being the first manufacturing site approved by the Food and Drug Administration (FDA) for immunocellular therapy production in the US.
Haematological oncology anticipates the wide scale use of chimeric antigen receptor (CAR) T-cell therapy in the treatment of ALL. ALL is a rapidly progressing and aggressive blood cancer affecting the individual’s white blood cells. It is commonly diagnosed in children and young adults and yet has a poor prognosis and outcome, hence the dire need for clinical development and therapy. In collaboration with the University of Pennsylvania, Novartis has successfully utilised CAR T-cell technology to outsmart cancer cells.
So, how does CAR T-cell therapy work? In a clinical setting, the patient’s blood is first drawn and white blood cells, including T-cells, are extracted. The T-cells are then genetically engineered to produce CAR proteins on the cell’s surface. The CAR T-cells, once infused back into the patient’s bloodstream, aim to attack and eradicate cancerous cells, thus resulting in prolonged remission. This dynamic therapy allows the modified cells to circulate the bloodstream mimicking normal blood cells. When in contact with cancerous cells, they release cytokines which are responsible for the recruitment of other cells that now also target the malignancy. Essentially, the modified T-cells are able to recognise and target antigens on cancerous cells in the bloodstream.
After centuries of endless research, promising results in clinical trials in 2017 enabled the FDA to approve the use of “Tisagenlecleucel”, which are humanised CD19 targeted CAR T-cells, branded as Kymriah™ for the treatment of relapsed or refractory B-cell ALL in children and adults under the age of 25. Kymriah™, being the first CAR T-cell therapy to obtain FDA approval, has revolutionised the research scene in oncology. This decision was influenced by the outcomes of three key clinical trials, one of which was deemed as the pivotal study. The JULIET trial has demonstrated that 64% of patients remain relapse-free with a 43% overall survival rate in patients with relapsed or refractory disease 18 months into the treatment. With the initial reservations that the National Health Service (NHS) had regarding the complexity of manufacturing and cost of Kymriah™ (which stands at a staggering £282,000 per patient), negotiations with Novartis and the National Institute for Health and Care Excellence has led to the availability of this therapy on the NHS to those eligible.
The beginning of a new era of innovative and effective chemotherapy is amongst us with individualised CAR T-cell therapy standing on the frontlines. Cancer survival rates in the UK are currently at the highest it has ever been, and the development and adoption of cutting-edge technology will be critical in the transformation of future cellular therapies.