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Acute myeloid leukemia in children, “PALM” was born, a network to find new therapies

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First: develop one new remedy for children with acute myeloid leukemia who resist standard therapies, who relapse and for whom there is a lack of effective solutions to date. Second: develop new diagnostic methods more accurate, able to help doctors better understand how the tumor is progressing. It was born with these two main goals “PALM” (Pediatric Acute Leukemia of myeloid origin), the new national network of specialized institutes coordinated in the field of oncohaematology by the children’s hospital Bambino Gesù and supported with more than three million euros by the Umberto Veronesi Foundation.Every year, about 70 children in Italy develop acute myeloid leukemiaa very aggressive blood cancer: the network’s activity will already contribute in the near future to optimizing the treatment of young patients, both in our country and in Europe, who follow the international protocol for the treatment of this rare haematological disease.

The project

The research and development project of innovative therapies for acute myeloid leukemia funded by the Umberto Veronesi Foundation will have one duration of 5 years and will theChildren’s Hospital Bambino Gesu how reference center, the Centralized Diagnostic Laboratory of the Oncohematologic Clinic of Padua, the Experimental Oncology Department of the European Institute of Oncology of Milan and the Leukemia Department of the MD Anderson Cancer Center (Houston, USA) as collaborating and contributing centers for the development of the project . The researchers of the network will be committed: all of themidentification of new molecular changes outcome predictors; the discovery of the mechanisms responsible for resistance to treatment or disease relapse and the implementation of clinical trials based on the use of CAR-Natural Killer cells for patients with this relapsed and/or refractory malignancy. “The Foundation’s goal has always been to maximize the chances of recovery and improve the quality of life of children affected by cancer – underlined Paul Veronesi, President of the Veronesi Foundation and Director of Surgical Breast Surgery at the European Institute of Oncology -. That’s why we’ve been funding scientific research and the best medical treatments for young cancer patients for years through the activation of treatment protocols that meet the highest international standards, we support many male and female researchers who have decided to dedicate their lives to the study and treatment of these pathologies and we carry out initiatives to raise awareness among the public and the competent institutions of the needs of adolescents with cancer. Because of all this, we decided to start this with the children’s hospital Bambino Gesu new state-of-the-art research platform for children with acute myeloid leukemia.

Acute myeloid leukemia

Acute myeloid leukemias are characterized by recurrent molecular changes that remain unidentified in a third of cases, just as the mechanisms leading to the development of recurrent and refractory forms to conventional treatments have yet to be fully elucidated. Thanks to next generation sequencing technologies (Next Generation Sequencing, NGS)available in the institutes of the network, however, some limitations can be overcome by obtaining new information about the disease: the molecular changes can in fact be predictors of good or bad prognosis; they can become indicators of sensitivity to treatments and facilitate the discovery of tumor targets that can be hit with targeted therapies. This type of study (molecular characterization) will be carried out for all cases of pediatric acute myeloid leukemia diagnosed in Italy in the centers of theItalian Society of Pediatric Hematology and Oncology (AIEOP), with whom the Umberto Veronesi Foundation has been working for years to support the costs of opening and managing treatment protocols in pediatric oncology units across Italy. “I am particularly pleased with the start of this project, which has all the characteristics to contribute significantly to the further improvement of the diagnostic and therapeutic approaches of this neoplasm in children and adolescents – he notes Frank Locatelli, head of the pediatric oncohaematology and cell and gene therapy department of the Bambino Gesù Children’s Hospital in Rome -. The collaboration between Aieop and the Veronesi Foundation represents a prototype model of how virtuous synergies of interaction between the scientific world and institutions whose purpose is to support research biomedical can be translated into initiatives of extraordinary importance for the treatment of oncological diseases and in this perspective, all researchers involved will do our utmost to honor the fiduciary investment of the Veronesi Foundation”.

CAR-Natural Killer Cells

The core therapeutic activity of the «PALM» network is lstart of the clinical trial (the first in Europe) of gene therapy with CAR-Natural Killer Cells for the treatment of acute myeloid leukemia that has relapsed or is resistant to conventional care. The preclinical study conducted at the Bambino Gesù Children’s Hospital concluded with promising results, the trial will start in late 2023 on a cohort of both pediatric and adult patients. The challenge is to replicate the results obtained with CAR cells in acute lymphoblastic leukemia in acute myeloid leukemia as well. In the new gene therapy designed for the Infant Jesus for this tumor, a population of the body’s immune cells other than T-lymphocytes was used: these are the allogeneic (ie, from a healthy donor) Natural Killer (NK) cells, then genetically reprogrammed to express the CAR (chimeric antigen receptor) on its surface, a molecule that intercepts the target of the tumor and causes the diseased cells to be destroyed. The use of engineered NK cells, rather than T lymphocytes, in the construction of immunotherapy against acute myeloid leukemia has been dictated by a series of scientifically proven advantages: unlike T lymphocytes, NKs do not trigger uncontrolled immune responses (the so-called «cytokine storm») nor graft versus host diseasethat is, they (by their very nature) do not affect the recipient’s tissues.

The initiative

Because of these properties, the NK of a donor can be used for the treatment of different people. In addition, it is possible to generate from a single cell sample via apheresis a sufficient number of CAR cells to cure many (at least a hundred) patients: a veritable “bank” of CAR-NK cells immediately available for infusion. In the gene therapy experiments with CAR-NK, conducted by the Child Jesus, researchers were observed on animal models high anti-tumor efficacy and significantly less toxicity than CAR-T cells, confirming the safety of the approach. “Great advances have been made in pediatric oncology in recent years, but there are still many issues that need to be addressed to improve the survival and quality of life of young patients,” he says. Clara Tonelli, Chairman of the Scientific Committee of the Umberto Veronesi Foundation -. We believe that the investigative activity carried out by the Internet alone does not make this possible increase the cure rates of young patients patients with acute myeloid leukemia, but which can also be applied to adult patients with leukemia”.From Monday 13 to Sunday 19 February 2023 it will be possible support the Umberto Veronesi Foundation for finance the research platform «PALM» right away SMS from a mobile phone or a call from a landline to 45598 to give children and young people with cancer the hope of fighting this terrible disease and growing up. Information support for the above fundraiser will be authorized by Rai per il Sociale on Rai’s radio and television channels, again from February 13 to 19.

Source: Corriere

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