CAR T-cell therapy (chimeric antigen receptor T therapy) comes under the branch of treatments known as immunotherapy - treatments that strengthen the immune system of patients so they can more effectively attack tumours and shrink or completely remove them from the patient’s body. T cells are immune cells whose role in the body is to search for and kill pathogens and cancers, but some cancer cells can ‘hide’ from normal T cells. This therapy involves genetically modifying T cells so that they have the ability to recognise and ‘hunt down’ these evasive cancer cells, in effect supplementing the body’s natural defences against cancer. The chimeric antigen receptor refers to the protein receptors which enable T cells to recognise and attach to specific cancerous, or diseased cells, which being targeted by the treatment.
The main use of CAR T cell therapy is for treating blood cancers. The NHS currently provides CAR T cell therapy for children with B-cell acute lymphoblastic leukaemia in those who have had a relapse following a bone marrow transplant, or if their leukaemia has not gone into remission after 2 rounds of treatment. It is also provided for adults who suffer from certain types of lymphoma. The treatment usually involves a blood sample being drawn from a patient via a central venous catheter to collect T cells, which are then modified in the lab and left to multiply until there are enough to infuse into the bloodstream. Chemotherapy takes place prior to the infusion to lower the number of T cells (lymphodepletion) in the patient’s body to ensure that their body does not reject the new CAR T cells.
Apart from cancer, CAR T cells can also be used to treat autoimmune diseases. In 2022 a clinical trial showed that CAR T cells relieved the symptoms of systemic lupus erythematosus, a disease caused by B cells which attack healthy tissues. After a few months, the new B cells that had formed no longer attacked the same tissues. There are also experiments taking place to investigate the effect of CAR T cells on asthma, rheumatoid arthritis and multiple sclerosis.
However, despite CAR T cell therapy’s benefits, there are serious side effects that can take place. The treatment can cause cytokine release syndrome, due to T cells stimulating cytokines (proteins that reduce inflammation and are part of the immune response) to be produced in large quantities. This can lead to fevers, low blood pressure and breathing difficulties. Other serious cases can lead to multi-organ failure. This could be treated with monoclonal antibodies (specifically tocilizumab), but some patients may still end up in critical conditions. One way to avoid this happening is to instead add CAR to the mRNA of the body’s T cells, which means CAR T cells can return to being normal cells after a certain amount of time, preventing the immune system from being overwhelmed.
CAR T cell therapy has also been touted as a “fountain of youth”, due to their ability to attack and destroy senescent cells: cells which have stopped ageing and replicating but cause inflammation in the body as they build up. Assistant Professor Corina Amor Vegas, of the Cold Springs Habor Laboratory in New York, led an experiment where mice were given CAR T cell therapy and their senescent cells were destroyed, giving them healthier lives without damaging any other tissues. Amor Vegas described that older mice rejuvenated when given the cells, whilst younger mice aged slower, an incredible breakthrough, especially since just one dose has lifelong effects due to the T cells’ memory. Should this effect be replicated in humans, this could have huge impacts on treatments for those living with chronic conditions, which require regular infusions and hospital treatments. These patients could instead have one CAR T cell treatment and then not require any other treatments for prolonged periods, improving their quality of life.
The versatility of CAR T cell therapy and its effectiveness as an alternative treatment for cancers and diseases, means it is a key area of current medical research. The 15 000 Americans cured of blood cancer as well as the children with leukaemia being pronounced cancer free after multiple relapses, would surely agree.3 In the fight against cancer and autoimmune disease that the medical world is currently waging, CAR T-cells look to be a reliable weapon to have in our arsenal.