CAR-T cells
Dr Robin Sanderson - Haematology
Created on: 10-31-2024
Updated on: 11-18-2024
Edited by: Jessica Wise
What are CAR-T cells?
CAR-T cells are genetically modified T-cells used as an immunotherapeutic treatment of certain cancers, specifically blood cancers like leukaemia and lymphoma.
T cells are a type of lymphocyte, a white blood cell that is part of the body’s immune system. T cells travel throughout the body inside the blood to attack abnormal or invading cells, including cancerous cells.
However, T cells can be unsuccessful in destroying cancer cells, due to cancer cells having their own defence and evasion mechanisms against white blood cells. This includes “disguising” themselves as nearby normal cells by displaying proteins, called antigens, on their surface, which misleads the T cells.
To convert them into CAR-T cells, these regular T cells are boosted and equipped with a receptor that will alert them to those antigens – the chimeric antigen receptor, or CAR.
In the UK, there are four CAR-T cell treatments available at the moment:
- axicabtagene ciloleucel
- brexucabtagene autoleucel
- lisocabtagene maraleucel
- tisagenlecleucel.
How are CAR-T cells made and used?
In order to make CAR-T cells, blood is withdrawn from a patient’s arm via an IV and fed through an apheresis machine to separate the T-cells from the blood. These cells are then taken to a sterile, specialised laboratory to be imbibed with the chimeric antigen receptors to create the CAR-T cells. Over a few weeks, they are cultivated and grown so that millions of these CAR-T cells can be reinfused into the patient’s body, where they can begin to attack cancer cells by binding to their antigen. After infusion, CAR-T cells will continue to multiply, becoming a “living treatment” for the patient over, ideally, many years.
Some patients may be recommended to undergo a course of chemotherapy treatment to prime the immune system before a CAR-T cell infusion.
Sometimes, a portion of CAR-T cells are cryogenically preserved for future use or study.
CAR-T therapy can be used in patient cases where other treatments, such as radiotherapy and chemotherapy, have not been successful.
In which cases can CAR-T cell therapy be used?
At the moment, CAR-T cell therapy is only effective for certain blood cancers:
- follicular lymphoma
- diffuse large B-cell lymphoma (DLBCL)
- chronic lymphocytic leukaemia (CLL)
- B-cell acute lymphoblastic leukaemia (ALL)
- high-grade B-cell lymphoma
- mantle cell lymphoma
- multiple myeloma
- primary mediastinal large B-cell lymphoma
Are there side effects to CAR-T cells?
There are possible side effects that can be caused by CAR-T cell infusion, namely cytokine release syndrome (CRS), which is when the level of cytokines in the blood is too high. Cytokines are chemical proteins that stimulate the immune system against pathogens and invading cells by triggering inflammation. However, in excess they can disrupt the nervous system, causing fever, nausea, headaches, confusion, loss of balance, rashes, palpitations, low blood pressure, and breathing difficulties.
CAR-T cells can also cause neurotoxicity, meaning brain side-effects. The exact cause is not entirely understood but within the first two weeks post-infusion, there can be a variety of symptoms such as word-finding problems, confusion, sleepiness, tremor, even seizures or unconsciousness. These side effects are transient and can be treated – which is why patients undergoing CAR-T therapy are monitored for some weeks so that complications like this, and others, can be addressed with haste.