The acronym, in itself, says very little, CAR-T. But there is much more to the tumor challenge behind the term. In the future and beyond.
CAR-T stands for Chimeric Antigens Receptor T-Cells. And these are already very important facts. For this reason, it is important to understand how these advanced therapies work, based on the modification and strengthening of T lymphocytes, which they are capable of. Identify and attack. tumor cells.
We are not talking about science fiction. These approaches are now a well-established reality in the clinical practice of several Italian centers. We are beginning to reap the benefits of these first years of use and administration of CAR-T therapies, which have become a new treatment paradigm for some. Blood tumors, aggressive and refractoryand a reason for hope for patients after so many failures. But the journey to the future has just begun.
How CAR-Ts work
CAR-Ts may be considered. One step ahead In personalized medicine in the field of tumors, and especially in neoplasms affecting blood cells. Today they represent a treatment option in patients in whom previous standard treatment strategies (chemotherapy and hematopoietic stem cell transplantation) have failed. Practically We start with T lymphocytes. It is taken from the patient’s blood. These are, in the laboratory, “armed” in such a way that they express a CAR receptor on their surface that helps them recognize and kill malignant cells, before they can even get into the patient themselves.
In this sense, these treatments combine at least three basic aspects. First it’s really about maintenance. intelligentas they identify targets expressed by tumor cells while sparing the patient’s non-diseased tissues. Then they act directly on the immune system, so they should be included.Immunotherapy. These are non-pharmacological treatments that are able to modify the drug resistance mechanisms that the tumor cells themselves implement in the most advanced stages of tumor disease.
Finally, comes the cure Cells. Moreover, from the same patient.
For this reason, these “special” units can. Staying in the body for a long time The patient in which they enter guarantees the mechanism of action over time and the ability to be reactivated each time the disease reappears. Let’s be clear. The use of these methods, which truly represents a frontier in treatment, can in rare cases be associated with the risk of events such as cytokine release syndrome, an overreaction of the immune response due to the infusion of modified T lymphocytes. is caused by Additionally, a decrease in B lymphocytes and antibodies and late cytopenias may persist. But we still face one. True innovationwhich is taking up more space than ever in therapy.
An immense development for a new frontier
While the number of authorized CAR-T cells in oncology and onco-hematology is increasing (according to the European Society for Blood and Marrow Transplantation-EBMT’s 2019 report on hematopoietic cell transplants, CAR-T therapies They increased by 650% 2017 competition) and scientific research in laboratories around the world is moving rapidly to find new and challenging targets to target, CAR-Ts as we know them today. The first step on a deeper evolutionary path And with answers to many questions. And for that we need to know.
This is the meaning of the action of AIL – the Italian Association against Leukemia, Lymphoma and Myeloma, which has decided to restart, from Milan, the CAR-T ‘Qvoyage’ – the future is already here”, a journey and on LINE campaign 2021, to inform Patients, family members, carers and specialistsand improve knowledge, access and management of treatment, taking into account the clinical experiences gained, the successes of the patients treated and the future areas of application.
When CAR-Ts are indicated
In Italy, according to very recent data, to date More than 1400 patients were treated.. This is a very large number, bearing in mind that the first administration dates back to 2019 and that for a long time only one center at the National Cancer Institute in Milan was authorized to perform this treatment. Currently they are approx. 30 authorized centers on national territory and 10 of them in Lombardy. Experience is also being gained in the use and administration of CAR-T therapies, and evidence and clinical data are accumulating.
“Already today, about 50% of acute lymphoblastic leukemias and 40% of large B-cell lymphomas are cured with this therapy – explains Paolo Corradini, Director of the Hematology Division, Melanier of the Fondazione IRCCS Istituto Nazionale dei Tumori (INT) Hematology, University of Milan and President SIE-Italian Society of Hematology – CAR-T cells One of the most innovative and promising strategies For the treatment of refractory hematological diseases. There is a lot of real-life data, derived from clinical practice at different centers in different countries, showing how CAR-Ts work very well in follicular lymphoma, and in multiple myeloma. also works just as well, although not with the same results as lymphomas. The response and survival data collected so far in refractory diseases are very encouraging, especially in Long-term survival. CAR-T proves that they work where nothing else was working.”
Treatment steps
“CAR-T has been introduced to the treatment panoramaof antineoplastic immunotherapy A revolutionary approach, which no longer involves the “simple” administration of a drug, but rather the proposal of a treatment program in sequential but distinct steps – Pier Angeliello, Hematologist, Hematology and Bone Marrow Transplant Unit, IRCCS in Milan San Rafael Hospital Report. Each of these steps is involved. Very complex process and interdependencies, which occur in physically separate locations, are managed by different teams and must occur at predetermined times, requiring logistical work that sometimes Goes beyond health care skills in the strict sense. Centers authorized for the administration of CAR-T are units specializing in cellular and genetic therapy, where pathways have been standardized that guarantee the chain of custody and identification from collection of material to re-infusion. These pathways are guaranteed by the Center’s complex accreditation process at an additional national and regional level.”
Infusion of CAR-T cells, for patients who have experienced prolonged and unsuccessful periods of treatment, Brings hope to life But it has to do with the unpredictable success rate or potential failure of that last treatment attempt. Psychological support, constant presence of specialists and nurses, hospitality in AIL accommodation are essential elements to support onco-haematological patients before, during and after CAR-T therapy.
Patient feedback
Research conducted in collaboration with Gilead and AIL Milano has made this clear. “It was based on interviews with 12 patients and 7 carers, it investigated the basic needs of onco-haematological patients with CAR-T cells and their carers – Sarah Alferi, Psychiatrist Researcher SSD Clinical Psychology, The IRCCS Foundation’s National Institute of Tumors states that gradients emerge as priorities: The so-called ‘existence’ requirementswhich is related to life and survival, or to the needs for which the patient wants to communicate, to believe and to hope that this major line of treatment will be good and if it does not have a positive outcome. , so there must be something else. Treatment options then emerge as aspirational needs. Informed in a comprehensive, compassionate and sincere manner, Otherwise, fear and uncertainty are fueled. After Maintenance requirements For which patients want improvements in basic services (psychological support, visits and checks near their residence) and the support of a world of associations to improve daily life. The need to not feel abandoned is strong and overwhelming. For their part, caregivers are more pessimistic and afraid to believe that another treatment attempt with CAR-T could have a happy outcome.”
Even for children. Research, Hope, Futurethese are the key words of CAR-T cell therapy that is promising a future for many children with blood tumors, sometimes refractory, mainly acute lymphoblastic leukemia. Research activity in the pediatric field to find gene therapies with the best safety, efficacy and durability profile is intense and extensive.
