The experimentation of a new therapy with genetically modified cells for relapsed forms resistant to conventional treatments begins at the Bambino Gesù, supported with over three million euros by the Umberto Veronesi Foundation
First: develop a new cure for children with acute myeloid leukemia that resists standard therapies, who relapse and for whom, to date, there is a lack of effective solutions. Second: develop new diagnostic methods more precise, able to help doctors better understand how the tumor evolves. With these two main objectives it was born «PALM» (Pediatric Acute Leukemia of Myeloid origin), the new national network of specialized institutes in the oncohaematological field coordinated by the Bambino Gesù Pediatric Hospital and supported with over three million euros by the Umberto Veronesi Foundation.About 70 children in Italy receive acute myeloid leukemia every yeara very aggressive blood cancer: the activity of the network will contribute, already in the immediate future, to optimizing the treatment of young patients, both in our country and in those in Europe which adopt the international protocol for the treatment of this rare hematological 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 involve theBambino Gesu Pediatric Hospital come reference center, the centralized diagnostic laboratory of the Oncohematological Clinic of Padua, the department of experimental oncology of the European Institute of Oncology of Milan and the Department of Leukemia of the MD Anderson Cancer Center (Houston, USA) as collaborating and contributing centers to the development of the project . The researchers of the network will dedicate themselves: allidentification of new molecular alterations outcome predictors; the discovery of the mechanisms responsible for resistance to treatment or disease relapses 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 who fall ill with cancer – underlines Paul Veronesi, president of the Veronesi Foundation and director of Surgical Breast Surgery at the European Institute of Oncology -. This is why we have been funding scientific research and the best medical treatments for young cancer patients for years through the activation of treatment protocols that comply with the highest international standards, we support numerous male and female researchers who have decided to dedicate their lives to the study and treatment of these pathologies and we implement initiatives to raise awareness among the public opinion and the competent institutions on the needs of adolescents with cancer. To all this we have decided to start this with the Bambino Gesu Pediatric Hospital new state-of-the-art research platform for children with acute myeloid leukemia.
Acute myeloid leukemia
Acute myeloid leukemias are characterized by recurrent molecular alterations which, in a third of cases, are not identified, just as the mechanisms that lead to the development of relapsing and refractory forms to conventional treatments remain to be fully clarified. Thanks to next generation sequencing technologies (Next Generation Sequencing, NGS)available in the institutes of the network, some limits can however be overcome, obtaining new information on the disease: the molecular alterations, in fact, can be predictors of good or bad prognosis; they can become indicators of sensitivity to treatments and facilitate the discovery of tumor targets to be hit with targeted therapies. This type of investigation (molecular characterization) will be performed for all cases of pediatric acute myeloid leukemia diagnosed in Italy in the centers of theItalian Association of Pediatric Hematology and Oncology (Aieop), with which the Umberto Veronesi Foundation has already been collaborating for years to support the costs of opening and managing treatment protocols in pediatric oncology wards throughout Italy. “I am particularly happy for the start of this project which has all the characteristics to contribute significantly to further improve the diagnostic and therapeutic approaches of this neoplasm in children and adolescents – he comments Frank Locatelli, head of the Pediatric Oncohematology and Cell and Gene Therapy Area of the Bambino Gesù Pediatric 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 that have the objective of supporting research biomedical can be translated into initiatives of extraordinary importance for the treatment of oncological diseases and, in this perspective, all of us researchers involved will lavish our best energies to honor the fiduciary investment implemented by the Veronesi Foundation”.
The CAR-Natural Killer cell
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 pre-clinical study conducted at the Bambino Gesù Pediatric Hospital concluded with significantly promising results, the trial will start at the end of 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 also in acute myeloid leukaemia. In the new gene therapy designed for the Child Jesus for this tumour, a population of defensive cells of the body other than T lymphocytes was used: these are the allogeneic (i.e. taken 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 tumor target and allows 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 give rise to uncontrolled immune reactions (the so-called «cytokine storm») nor to graft versus host diseasethat is to say that (by their nature) they do not attack the recipient’s tissues.
The initiative
Due to these characteristics, the NK of a donor can be used for the treatment of different people. Furthermore, from a single cell sampling via apheresis it is possible to generate a number of CAR cells sufficient to cure many patients (at least a hundred): a real “bank” of CAR-NK cells immediately available for infusion. In the experimentation of gene therapy with CAR-NK conducted by the researchers of the Child Jesus on animal models were observed high antitumor efficacy and significantly less toxicity than CAR-T cells, confirming the safety of the approach. “Great strides have been made in the field of pediatric oncology in recent years, but there are still many problems to be solved to improve the survival and quality of life of young patients – he says Clare Tonelli, President of the Scientific Committee of the Umberto Veronesi Foundation -. We believe that the research activity carried out by the Internet will not only allow increase the healing 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 per finance the «PALM» research platform with a 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 aforementioned fundraising campaign is authorized by Rai per il Sociale on the Rai radio and television channels, again from 13 to 19 February.
January 24, 2023 (change January 26, 2023 | 10:57 am)
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