News from the scientific world

What is the CAR-T therapy?

This week I will take a break from the “brain facts” category and, consequently, from the description of the different neuromodulators our brain use (you can find a quick description of what a neuromodulator is here and a description of serotonin, oxytocin, adrenaline and dopamine by clicking on their names) to talk about a “news from the scientific world”, Italy edition: the CAR-T therapy finally got approved by the Italian agency of drugs (Aifa) and will now be available for some lymphoma and leukemia cancer patients that fulfill certain requirements. I know it may seems a small news, since only some of the patients would be allowed to use this therapy, but if we consider that some of the requirements for these patients are the resistance of the cancer to all the therapies and treatments or the reappearance of the cancer after the initial response to the standard treatments, it is a huge news that can bring hope to people that might have lost it, after having tried everything available to them to fight cancer.

But let’s talk about this innovative therapy and where its strength lies in.

The standard treatments used to eradicate cancer are surgery, chemotherapy and radiation therapy. However, over the last several years, immunotherapy (a therapy that involves the use of a patient’s own immune system, after having strengthen it) has emerged. Indeed, the first clinical trials were restricted to few cases and in particular to the ones that presented advanced blood cancers. However, these few trials captured the attention of clinicians, researchers and the general public due to the remarkable responses they produced (both in adults and children) for whom all other treatments had failed and/or stopped working.

As I already mentioned above this therapy involves the use of a patient’s own immune system: his T-cells (one of the many different types of cells that belongs to the immune system, considered the workhorses due to their critical role in directing the immune response and killing the infected cells) are drawn from the patient’s blood and separated from the other types of cells. The isolated cells are then genetically engineered using a disarmed virus, to express receptors on their surface called chimeric antigen receptor (CAR). These receptors do not exist naturally, they are synthetic molecules that allow the newly engineered T-cells to recognize the tumor cells and organize the immune response in order to kill the cancer cells. The CAR-T cells, ready to recognize and fight the cancer cells, are expanded and then infused into the patient: if all goes as planned, the engineered cells can now start eliminating the cancer cells from the patient (see below for a schematic of the therapy).

Schematic of CAR-T therapy steps. From cancer.gov

As good as it looks on paper, like all treatments and therapies, and in particular the ones against cancer, the CAR-T therapy has several, and sometimes fatal, side effect that should be taken into account. One of these dangerous side effects is the cytokines release syndrome (CRS). During their normal line of action, T-cells release cytokines, chemical messengers to stimulate and direct the immune system towards the threat. In the CRS, these chemical messengers are released rapidly and in a massive amount, leading to high fever and drops in blood pressure. Since the CRS is considered a sign of the activity of the T-cells and, therefore, an “on-target” effect, patients experiencing it are provided with supportive therapies that rapidly solve the issue in most patients. Other side effects, this time “off-target”, involve the swelling in the brain, unfortunately seen in some of the larger clinical trials (even though the problem seems to be limited) and confusion or seizure-like activity (that, fortunately, in nearly all patients is a short lived and reversible problem).

Having talked about the pros and some of the cons, I want to underline that researchers are still cautious and we are still in the early days of this new treatment, raising questions on whether this therapy could also be used against solid tumors like breast cancer. Nevertheless, many progress have been made and scientist made huge efforts in order to develop a better understanding of how these therapies work in patients and translating this knowledge into great improvements in how these treatments are developed and tested.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s