LivingCAR-T: Living Therapies to Treat Cancer

CAR-T: Living Therapies to Treat Cancer

Can you imagine that your own immune cells could be reprogrammed to attack cancer cells throughout the body? Well, it is already a reality, and it is being applied in Spain. We are talking about CAR-T, chimeric antigen receptor (CAR) T-cell therapies. They allow treating with great success several types of very aggressive blood tumors, where the estimated survival does not reach seven months of life.

This new generation of living cancer therapies, proclaimed by the American Society of Clinical Oncology Breakthrough of the Year in 2018, involves a complex process, to say the least. First, T cells or lymphocytes – a type of white blood cell – are removed from the patient and taken to the laboratory, where they undergo a genetic change to attack cancer cells. These reprogrammed immune soldiers are then grown in large numbers and injected into the patient.

Currently, there are two approved therapies used in our country: the CAR-T developed by the company Novartis and by the pharmaceutical company Gilead. Both, intended to treat several very aggressive types of non-Hodgkin lymphoma, present really encouraging results.

For example, in the clinical trial conducted with the drug developed by Gilead, 74% of patients with B-cell non-Hodgkin lymphoma treated with a single infusion of these cells had improvement, while 54% experienced remission. total cancer. After two years of follow-up, most of the patients were still alive. In the Novartis therapy clinical trial, targeting children and youth with B-cell acute lymphoblastic leukemia, 83% of individuals responded to treatment. In three out of four patients, there was no relapse after six months. These are just two milestones in a research career in which Spain is a benchmark at the European level.

The Ministry of Health has launched the National Plan for Advanced Therapies, which, in addition to accelerating the arrival of these treatments to the patient, aims to promote ongoing public investigations. In fact, the Hospital Clínic de Barcelona has just started an advanced phase clinical trial, in which other centers participate, to develop a public CAR-T.

Where are these drugs administered?

The Ministry of Health has designated eleven reference hospitals spread over five autonomous communities: the Valencian Community, Catalonia, Castilla y León, Andalusia and Madrid. These are centers that have had to prove their ability to treat patients and that have specific units designed to offer these therapies effectively.

Patients who do not have an accredited and available hospital in their community will be referred to the closest one. At the moment, CAR-T therapies are applied exclusively to blood tumors. And although research is being done to treat other types of conditions, the challenge seems complicated. “The big problem and the biggest difference between the blood tumor and the rest of cancers is that while in the first one a monogenic alteration –that is, a very specific one– marks the entire development of the tumor process, in the second it does not a single alteration can be identified so precisely, ”explains Jesús GarcíaFoncillas, director of the Oncohealth Institute of the Jiménez Díaz Foundation, in Madrid.

But, as the expert tells us, the path is already opening. “ It is still a reality in growth and construction, which starts with the identification of priority targets in non-blood tumors. In this way, immune cells that recognize this specific structure as something harmful can be built ”, indicates García-Foncillas.

An expert tells us about CAR-T therapies

Jose María Moraleda Jiménez is coordinator of the Cell Therapy Network of the Carlos III Health Institute and professor of Medicine at the University of Murcia. This tells us:

CAR-T therapies are a form of disruptive and innovative cell therapy that falls within the so-called personalized medicine. It consists of the transplantation of T lymphocytes, which are obtained from the patient himself and modified in the laboratory using genetic engineering techniques so that they express on their surface an artificial –chimeric– receptor directed against a specific ligand –signal molecule– of a tumor cell.

When receptor-ligand binding occurs, the T lymphocyte becomes activated, multiplies logarithmically, and kills the tumor cell by releasing molecules that cause direct cell damage. Before transplantation, patients should receive treatment to facilitate CAR-T implantation and expansion.

Although they have serious side effects and their production is complex and expensive, CAR-T therapies are considered one of the greatest therapeutic advances in recent decades due to their excellent results in patients in near-terminal phases.

Children with acute B-cell leukemias that do not respond to chemotherapy have lasting responses of 50% to 70%, and adults with refractory aggressive B-cell lymphoma from 40% to 60%. Currently, these therapies are being investigated to treat solid tumors, autoimmune and infectious diseases, in what can be considered a new therapeutic revolution.

Article written by Marta Riesgo

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