CAR-T: understand cancer therapy – 05/30/2023 – Health

Last Monday (29), researchers from the Hospital das Clínicas in São Paulo announced the total remission of a patient’s cancer one month after using CAR-T therapy.

Paulo Peregrino, 61, who had non-Hodgkin’s lymphoma for 13 years, participated in a study by the Center for Cellular Therapy, which includes scientists from USP, the Faculty of Medicine of Ribeirão Preto, the Blood Center Foundation and the Butantan Institute.

CAR-T uses immune system cells (known as T lymphocytes) taken from the patient and genetically modified to recognize and attack tumor cells. The therapy has been used to treat some types of cancer.

The therapy was approved for so-called compassionate use in Brazil. This practice is adopted when there is no other approach possible and therapies still under study are used to try to save the patient’s life.

In the United States, the FDA (Food and Drug Administration) has authorized treatments of this type since the early 2010s.

See below what the technique is, in what situations it has been used, what types of cancer it is recommended for and how to find it in health services in the country.

How does CAR-T cell therapy work?

CAR-T cells (chimeric T cell antigen receptor) are immune system cells (known as T lymphocytes) taken from the patient. They are genetically modified to recognize and attack tumor cells and then reintroduced into the patient. Thus, they become more effective in identifying the focus of cancer and attacking it.

The technique derives from studies with cell therapy, which began in the 1950s with bone marrow transplantation. Similarly, CAR-T therapy consists of “transplanting” the patient’s modified immune system in order to help him in the immune response. Additionally, CAR-T cells carry information about the target to be attacked, in this case tumor cells.

Experimental CAR-T therapy uses the patient’s own cells, but there is research with modified donor cells (called “allo-CAR-T”, derived from “other”). At the moment, there is no authorization for the use of donor cells in Brazil.

In general, patients with a very aggressive cancer, or who have a weakened immune system, have more difficulty generating their own immune response, which is why CAR-T therapy can be an important ally.

As therapy is only used for so-called compassionate use, when no other treatment is available, responses are often mixed. In the case of the Nutera (Advanced Therapy Nucleus) study, the health status of most patients is already severely impaired.

“We’ve had some transient responses so far, others that have lasted for more than a year, but all patients have had some type of response. And that’s considering that their clinical conditions, when they arrive at our center, are not the best” , says head professor of hematology at USP in Ribeirão Preto and former director of the Butantan Institute Dimas Tadeu Covas.

What types of cancer is it recommended for?

Currently, CAR-T therapy has been successful in the treatment of some types of cancer of the blood system, such as lymphomas, leukemias and myelomas, but there is no proof of effectiveness against solid tumors. In these cases, chemotherapy, radiotherapy or treatments such as immunotherapy tend to be more effective.

There are several ongoing clinical studies in the world to evaluate the use of CAR-T cells in solid tumors, such as breast, ovary and lung, but these studies are still in the laboratory test phase (animals) or in an initial phase in humans. This is innovative research that seeks to develop CAR-T cells that specifically respond to signals emitted by some of these tumors, as in the case of the mesothelin protein, released by some types of ovarian cancer.

More research, however, will be able to tell if they will work in the human organism. “The big difference is that ‘liquid’ tumors or hematological cancer are easily accessed by the bloodstream, while solid tumors are encapsulated, so the results are more promising in this type of cancer”, completed the doctor.

When did it start to be applied in Brazil?

So far, 13 patients have been included in the experimental study developed at Nutera, two of which were treated at the HC in São Paulo and the other 11 at the Blood Center in Ribeirão Preto. The first patient to receive the therapy, in 2019, was a 62-year-old man with non-Hodgkin’s lymphoma, who had remission about 40 days after treatment, but he suffered a domestic accident and died at home due to head trauma .

How many cases of remission are attributed to cell therapy?

Remission is when there is no longer a tumor focus in the body, indicated by imaging tests (such as computed tomography) or by biochemical analysis (such as anatomopathological examination – biopsy).

In Brazil, approximately 69% of patients had remission 30 days after therapy. This number is consistent with international data, which show that about half (50%) of patients have a complete cure of the disease after five years of therapy.

Cure, according to the international clinical protocol, is when there is no more tumor focus and remission remains five years after therapy. To date, no patient has been included in the study with follow-up longer than one year and four months. Therefore, there has not been any case of cure yet described.

In December of last year, there was the announcement of the case of a 13-year-old girl who had remission of a leukemia considered “incurable” after the use of CAR-T. She received the modified cells from a donor, a technique not yet available in Brazil.

“We are also studying the so-called use of CAR-NK cells [de matadoras naturais, ou natural killers]which could be produced from a universal ‘off-the-shelf’ donor, as medicines available directly to the consumer are called”, explains Vanderson Rocha, physician responsible for the treatment of the two patients at HC de São Paulo and coordinator of the therapy center Rede D’Or’s national cell phone.

Is the treatment already available in the SUS?

The treatment is available free of charge for patients who want to be included in the compassionate use study, at the Cellular Therapy Center, when there is no other method that can be used and at least two types of conventional therapies have already been performed without successful remission.

The scientists will start a clinical study with about 75 patients by the end of the year. After the clinical phase, if approved, the product can be produced at the two Nutera manufacturing centers —one in São Paulo, still awaiting opening, the other in Ribeirão Preto— and offered to all SUS patients. Authorization for the production of the drug at the Butantan Institute must be granted by Anvisa (National Health Surveillance Agency) after the completion of clinical studies and factory analysis.

What about the private network? What the value?

Regarding the private network, there are two products already with commercial authorization in the country: Yescarta, from Gilead Sciences, and tisagenlecleucel, from Novartis. The cost of the product averages R$ 2 million. There is no provision for incorporation of the drug into the SUS or the ANS list, which determines which procedures and drugs are authorized to be fully covered by health plans.