An all-Italian experimentation to knock out acute myeloid leukemia, using cells of the immune system enhanced in the laboratory thanks to gene therapy, the CAR-Natural Killer (NK). And, at the same time, an international mega-project to shed light on this complex and still partly unknown disease, of which there are many forms and with very different responses to the treatments available today. These are the objectives with which PALM was born, the national network of institutes specialized in oncohematology coordinated by the Bambino Gesù Pediatric Hospital and supported by the Umberto Veronesi Foundation, which aims to revolutionize treatment in the field of acute myeloid leukemia.
What is the acute myeloid leukemia suffered by Sinisa Mihajlovic
CAR-NK: a new type of immunotherapy
Let’s start with the experimentation, which is based on the same principle as CAR-T therapies but which, instead of engineering the patient’s T lymphocytes in the laboratory, uses other cells of the immune system: the natural killers (NK). “This type of cells can be transplanted even without compatibility with the donor, because they have the ability not to attack the recipient’s tissues – he explains to Salute Concetta Quintarelli, head of the Tumor Gene Therapy Unit of the Bambino Gesù Pediatric Hospital in Rome and professor at the Federico II University of Naples: “They also have a natural ability to recognize the cells of acute myeloid leukemia”. This natural recognition ability will be enhanced in the laboratory by researchers thanks to gene therapy techniques that will “mount” a receptor capable of recognizing a target on diseased cells once re-infused into the patient. This is CD123, explains the researcher, a molecule expressed above all on cancer stem cells, those that feed the tumor. And it is the first time in Europe that NK cells are used in humans against acute myeloid leukemia.
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The advantages of natural-killer cells against tumors
Thanks to NK tolerance, unlike the more traditional CAR-T cells, these cells can also come from different people (healthy donors). And the availability of allogeneic transplants, with ready-to-use therapies in biobanks, would be an advantage above all against this type of leukemia: “Patients with AML, precisely because of the acute nature of the disease, cannot wait days for preparation of cells in the laboratory, as is the case for CAR-T cells – resumes Quintarelli – Allogeneic CAR-NK cells would save precious time”. Not to mention that, according to the data already collected at the preclinical level, NK cells have shown less toxicity than CAR-T cells. “The start of the trial is expected within the year, and will involve the Bambin Gesù for pediatric patients and the European Institute of Oncology for adults”, concludes Quintarelli.
Blood cancers, the point on new therapies
by Tiziana Moriconi
Acute myeloid leukemia
A rather varied disease, to date this form of leukemia – which affects around 2000 people every year in Italy, 70 of whom are children – is only partially known from a molecular point of view. This prevents us from understanding its evolution, responses to treatments and the development of new therapies. To the point that today about 40% of all patients relapse after the first lines of treatment and stem cell transplants. “Chronic myeloid leukemia presents different subtypes of the disease, with different prognoses, associated with a different genetic basis – explains the expert – which is why a good part of the activity of the PALM network will be dedicated to understanding the molecular basis of the different classes of risk”. In fact, a central part of the project will be the molecular investigations carried out on diseased cells to identify the basis of resistance to therapies and discover new predictive indicators of their outcome. In detail, the heart of the PALM project will be the molecular characterization of all cases of acute myeloid leukemia in children diagnosed in the AIEOP – Italian Association of Pediatric Hematology and Oncology Centers.
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A solidarity number to contribute to research
From Monday 13 to Sunday 19 February 2023 it will be possible to support the Umberto Veronesi Foundation to finance the “PALM” research platform with an SMS from a mobile phone or a call from a landline to 45598. “The Veronesi Foundation’s goal has always been to maximize the chances of recovery and improve the quality of life of children who get cancer – he concludes Paul Veronesi, President of the Umberto Veronesi Foundation, full professor in General Surgery at the State University of Milan – This is why we decided to launch this new cutting-edge research platform with the Bambino Gesù Pediatric Hospital for children with acute myeloid leukemia”. Together with Bambin Gesù and Ieo, the centralized diagnostic laboratory of the Oncohematological Clinic of Padua and the Department of Leukemia of the MD Anderson Cancer Center (Houston, USA) are part of the PALM project. But more generally, the PALM project aims to establish a series of European collaborations to optimize treatment protocols for patients with AML even outside the Italian borders.