The future has begun
The FDA has just approved the first chimeric antigen receptor (CAR) T cell therapy offered by Novartis and the second licence for Kite’s CAR-T treatment is expected very shortly. Tisagenlecleucel-T, the product which Novartis calls Kymriah, has received clearance for use in paediatric and young adult patients (age 3 to 25 years) with relapsed or refractory acute lymphoblastic leukaemia (ALL).
Expectations for this new treatment in oncology are high and many patients refilled with hope; some medics go as far as to herald a new dawn in cancer therapy. Should we get excited about CAR-T or is it yet another cancer treatment for the record books of extortionate costs, ending up doing more harm than good?
CAR-T therapy is undoubtedly a novelty in cancer treatment. What makes it promising is that live cells are being used. What makes it unique is that each patients’ own cells are being used. What makes it revolutionary is the that these T cells are genetically engineered to fight cancer. Three high-tech approaches in one Therapy.
“A cell is more powerful to fight disease than any drug will ever be” – from this premise derive all endeavours in immunotherapy which have been driving the Research in T cell receptors since the late 80ies. Encouraging outcomes, however, have only been demonstrated in recent trials, reaching unanimous approval by the FDA. With rekindled interest in T cell therapy, investors are likely to open the money tap to exploit this avenue further.
The concept of T cell therapy
In most cancers, human cells have become malignant through several mutations, which prevent them from self-death (apoptosis) and promote them to uncontrolled multiplication, they have also managed to escape any immune response against them. They can hide from the immune system which does make sense, after all, they derive from tissue that is recognised as own. CD19 is a biochemical feature, or antigens to be precise, that is particular to the blood cancer called ALL. Tisagenlecleucel-T provides a receptor that binds explicitly (hence attacks) on the CD19 molecule.
How exactly is CAR-T therapy produced?
T cells are filtered out from the patient’s blood; a process called apheresis which is available in most clinics. These blood cells are sent to a specialised laboratory to be treated for 15 to 20 days before they return modified and multiplied.
Two major steps happen at the laboratory
First, the T cells are genetically engineered. In other words, a gene, which codes for a particular receptor (the chimeric antigen receptor), is inserted into the T cell’s DNA.
In a second step, these newly armoured T cells are multiplied into many million little fighters.
The finished treatment will undergo several stages of quality testing before it is ready for use
What are the side effects?
Tisagenlecleucel-T binds to all CD19 antigens; this receptor exists not only on cancerous B cells but also on healthy B cells. These play an essential role in fighting infection and producing antibodies against many communicable diseases. Treatment with Tisagenlecleucel-T can, therefore, cause an increase in infectious disease.
Other side effects that have been observed are CRS (cytokine release syndrome) and neurological disorders. CRS is is a type of systemic inflammatory response similar to that found in severe infection characterised by hypotension, pyrexia, and rigours. The patient feels unwell, as if in a state of high fever. It can be treated with the interleukin-6 antagonist tocilizumab. Neurological effects during the trial phase included encephalopathy, seizures, delirium, hallucinations, cognitive disorder, depressed conscious level of consciousness, mental status changes, muscular weakness, and dysarthria – all of them were reversible and could be treated with steroids.
What will the future bring?
By stepping into the commercial sphere, T cell therapy is consolidating its presence in oncology which will undoubtedly lead to further research, trials and investments.
CAR-T therapy might help to improve the tarnished reputation of ‘genetically modifying’.
Today, I am joining in the celebrations of this milestone and believe that CAR-T therapy will play a significant role in the future of cancer treatment. It will need further years of tweaking, but the prospect that one day a T cell receptor can be engineered to detect Antigens of an individual cancer fills me with enormous hope