FAQ

CAR-T cell therapy emerged in the United States and began to be applied experimentally in terminal cancer patients in the early 2010s. In 2017, the positive results led the Food and Drug Administration (FDA) to unanimously approve the use of CAR-T therapy to fight cancer. In 2018, CAR-T cell therapy won its discoverers, James P. Allison and Tasuku Honjo, the Nobel Prize in Medicine.

In Brazil, CART- cell therapy is developed at the Center for Cell-based Therapy of the School of Medicine of Ribeirão Preto, USP. The first Brazilian volunteer, who received the experimental treatment two years ago, achieved complete remission of an end-stage lymphoma. Other patients who opted for treatment also experienced remission. To date, cell therapy has been shown to be highly effective against cases of lymphoma and acute lymphoblastic leukemia, two types of blood cancer.

The CAR-T technology is a type of immunotherapy that uses T lymphocytes, cells of the immune system responsible for fighting pathogens and killing infected cells. The treatment consists of removing and isolating T lymphocytes, activating them, “reprogramming” them to be able to identify cancer cells and then infusing them back into the individual's body. Then, the modified defense cells come back stronger to eliminate the tumor cells. This entire process, from cell collection, modification and administration to the patient, can last around 60 days.

CAR-T is what the cells used in therapy are called. The name CAR-T comes from the union of two concepts: CAR is the acronym for chimeric antigen receptor and T comes from T lymphocytes, the body's defense cells. In cell therapy, the T lymphocyte is altered to express CAR receptors on its surface and become even stronger in fighting cancer – it changes from being a T cell to becoming a CAR-T cell.

CAR-T cell therapy is considered one of the most innovative treatments in medicine and represents a revolution in cancer treatment. It is highly complex and personalized, as it uses the patient's own defense cells to fight the disease.

After the blood is collected, the doctor determines cell parameters to separate only the cell group of interest (the T cells). Then, the researchers apply a reagent that stimulates the activation of these cells. Once the T lymphocytes are activated and multiplied, they are placed in contact with a lentiviral vector – a modified virus incapable of causing disease. This vector contains the genetic information of a receptor that recognizes the antigen called CD-19, which is expressed on the surface of tumor cells.

As it contains the genetic information of the CD-19 receptor, the vector makes the T cell express it on its surface, giving rise to CAR-T cells that will be used in therapy – and which will bind to the CD-19 present in tumor cells. The product is frozen and undergoes rigorous quality control tests, before being infused into the patient in a process similar to blood transfusion. Back in the bloodstream, this set of CAR-T cells recognizes and binds to cancer cells, inducing cell death.

Soon the protocol for a clinical study on CAR-T cell therapy will be submitted to the Brazilian Health Regulatory Agency (ANVISA). Phase 1 of the study is expected to begin in October 2022. 30 blood cancer patients – specifically, B-cell non-Hodgkin's lymphoma – will be eligible to participate.

As it is still experimental and a relatively recent discovery – the first successful cases took place about ten years ago in the United States – CAR-T cell therapy is not available on a large scale and is very expensive: it can cost US $500,000 per patient.

The partnership between Butantan, the Ribeirão Preto Blood Center and USP aims to expand access to treatment and ensure that it reaches the Brazilian Unified Health System (SUS). Until then, the therapy was only offered at the Center for Cell-based Therapy of the School of Medicine of Ribeirão Preto, USP, and on a small scale – one patient undergoing treatment at a time. The creation of two cell therapy units (one in Ribeirão Preto and another in São Paulo) will increase this capacity to up to 300 patients per year.

Moreover, this will be the first 100% national production center of cell therapy for cancer, coordinated by non-profit institutions, which facilitates cost reduction and the inclusion of treatment in the Unified Health System (SUS). Today, Brazil has two CAR-T therapies registered by the Brazilian Health Regulatory Agency (ANVISA), one from Novartis and the other from Janssen. However, its high cost of US$ 500,000 per application limits its accessibility, and the production of CAR-T cells takes place abroad.

Butantan offers its production capacity, experience with processes conducted under good manufacturing practices, clinical development and delivery of biopharmaceuticals to try to reduce the cost of therapy as much as possible and make it available to the Brazilian population free of charge through the Unified Health System (SUS).