CART cells are the patient’s own T-lymphocytes (autologous T-lymphocytes) that are genetically modified in the laboratory so that they are capable, once infused back into the patient, of destroying the patient’s tumor (malignant) cells.
These cells have what is called a chimeric antigenic receptor on their surface. This means that one of the parts is able to bind to a surface antigen characteristic of the tumor cell and the other part is responsible for activating the T-lymphocyte once infused into the patient so that it, in turn, activates other lymphocytes and other cell types.
In which cases is it indicated?
Currently in Spain we can use CART cells outside of clinical trials in patients under 25 years of age diagnosed with acute B-lymphoblastic leukemia, which has proven to be refractory to other previous standard treatments. Also in patients with certain types of aggressive B lymphomas (mainly diffuse large B-cell lymphoma) who have failed at least two lines of prior chemotherapy.
However, other constructs will soon be approved for other oncohematological diseases such as multiple myeloma or mantle cell lymphoma.
How is it administered?
CART cells are administered intravenously, through a central venous catheter. The patient is prepared beforehand, with a treatment called lymphodepletive, which aims to allow the CART cells to act better and be more potent after their infusion.
What are the benefits of this type of therapy?
At present there is no very long follow-up of patients treated with CART cells outside clinical trials. What we do know is that, both in patients with B lymphomas and in patients with B acute lymphoblastic leukemia, it manages to cure a percentage that before its development were considered incurable with standard treatment strategies.
Therefore, they offer a curative option in patients who previously had a very poor prognosis and were considered incurable.
What are the possible side effects of CARTs?
The infusion of CART cells is associated with two side effects characteristic of this procedure, which appear in a non-negligible percentage of patients, and which may pose a significant risk to them.
Cytokine release syndrome, which is due to the rapid and massive activation of many T lymphocytes and other accompanying cells. This is characterized clinically by fever, hypotension, need for oxygen therapy and vasoactive drugs and sometimes involves transfer to the Intensive Care Unit.
Neurological toxicity may also appear in the first days after infusion of CART cells. It is characterized by reduced symptoms (difficulty in writing, memory loss, motor deficits…) until eventually reaching coma.
There are treatments for these two types of side effects: tocilizumab and corticosteroids.
Patients treated with CART cells are very immunosuppressed patients who are at risk of developing infectious complications. Sometimes hematologic recovery after administration of lymphodepletive chemotherapy is not complete and the patient is subject to the need for periodic transfusions and sometimes patients must be treated with immunoglobulins periodically.
Are there any risks for the patient?
All the side effects discussed in the previous point can put the patient at risk. Overall, the mortality associated with the administration of CART cells is low, less than 5%, similar to that associated with autologous transplantation.