CAR-T therapy: what it is, how it works, and who it can help
Written in association with:CAR-T therapy is an emerging type of immunotherapy that is being implemented for the treatment of certain cancers. In this article, Dr Robin Sanderson, a consultant haematologist with expertise in haemato-oncology, explains this groundbreaking treatment.
What is CAR-T therapy?
CAR stands for “chimeric antigen receptor”, and it is a treatment that involves a “reprograming” of the T cells, which are a kind of white blood cell called lymphocytes that protect the body from infection and invasion.
T cells are a part of the body’s immune system, developing from stem cells in the bone marrow. They travel through the blood to find and kill abnormal cells. However, cancer can be difficult for the body and white blood cells to fight against because they cannot consistently recognise the cancer cells as malicious. Thus, CAR-T therapy was developed in order to “train” the T-cells to be more effective against cancer.
In the UK, there are different CAR-T therapies available including: axicabtagene ciloleucel, brexucabtagene autoleucel, lisocabtagene maraleucel and tisagenlecleucel.
How does CAR-T therapy work?
Some T cells are removed from the blood that has been extracted from the patient in a process called leukapheresis, and then genetically modified in a laboratory, which can take up to three weeks. Specialists inset the T cells with a new gene, transforming them into CAR-T cells, which are then reinfused into the body via a drip.. Once released back into the bloodstream, they attack and can kill cancer cells as they are now able to detect them. Patients are closely monitored for the weeks after CAR-T therapy to track progress and keep an eye out for complications, which requires hospital specialists.
CAR-T has been used in cases where all other treatments have failed, providing new hope for cancer patients. Because CAR-T cells will continue to circulate in the blood they act as a long-term, “living” treatment against cancer.
Who can be treated with CAR-T therapy?
At the moment, CAR-T therapies are only effective against certain blood cancers, specifically lymphoma, leukaemia and myeloma, and only in some cases.
The kinds of blood cancers it can be used for are:
- diffuse large B-cell lymphoma (DLBCL)
- primary mediastinal large B-cell lymphoma
- high-grade B-cell lymphoma
- mantle cell lymphoma
- follicular lymphoma/marginal zone lymphoma
- chronic lymphocytic leukaemia
- B-cell acute lymphoblastic leukaemia (ALL)
- multiple myeloma
CAR-T therapies tend to be explored as an option after more common treatments have proven ineffective, but this is an established technique although with some serious possible side effects, such as too many cytokines in the blood (cytokine release syndrome or CRS), which are a chemical that stimulates the immune system but in excess, they can cause high fever, breathing and cardiac issues. It can also disrupt the nervous system, causing headaches, seizures, confusion and loss of consciousness, comprehension and speaking difficulties and rarely seizures. That’s why it is only recommended for specific cases and under very specialist care.
As an example, here are some of the circumstances that would be eligible for CAR-T therapy:
- children and young people up to 25 years old with ALL (tisagenlecleucel)
- adults with DLBCL or primary mediastinal large B-cell lymphoma whose lymphoma has continued to grow after one or two prior treatments, such as chemoimmunotherapy (axicabtagene ciloleucel and lisocabtagene maraleucel)
- Adults with mantle cell lymphoma, whose lymphoma has continued to grow after two prior treatments (brexucabtagene autoleucel)
- Adults aged 26 and over with ALL, where treatment has not worked, or the ALL has come back after treatment (brexucabtagene autoleucel)
- Adults with follicular lymphoma and marginal zone lymphoma, which has returned after two prior treatments (axicabtagene ciloleucel and lisocabtagene maraleucel)
- Adults with chronic lymphocytic leukaemia who have previously been treated with BTK inhibitors and BCL2 inhibitors (lisocabtagene maraleucel)
- Adults with multiple myeloma
If you would like to know more about CAR-T therapy, or other blood cancer treatments, consult with Dr Sanderson via his Top Doctors profile.
