SHORTLY after the approval of the first CAR-T therapies, Italy launched its bet, with the start of the research project “CAR-T” promoted by the Parliament. There are several Italian centers that have been working in the field for some time and our country aims to expand the possibilities offered by these new cancer therapies. On several fronts: both clinical, managerial and legal ones. And after a year of activity, despite the complications imposed by the pandemic, the first results arrive.
In recent days, in fact, the Alliance Against Cancer Network, which coordinates the project, and the Ministry they had announced the positive results for the first three children with treatment-refractory acute lymphoid leukemia with B-cell precursors (ALL-BCP), treated with freshly produced CAR-T cells at the Pharmaceutical Workshop of the Bambino Gesù Pediatric Hospital (OPBG ) From Rome.
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The advantages of “fresh” CAR-T
CAR-T cells are T lymphocytes taken from the patient and engineered to learn to attack the cancer – thanks to a receptor capable of recognizing specific tumor antigens – and finally reinfused into the patient himself. In fresh production, the engineering process takes place directly in the laboratory of the hospital where the patient is located, without the need to freeze the lymphocytes and send them overseas, as is usually the case.
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Optimizing the fresh production of these cells is one of the objectives of the project, in particular in Work Package 1, as he explains Ruggero De Maria, Deputy Scientific Director of the Gemelli Polyclinic and President of the Alliance Against Cancer: “The fresh production, in this case the one carried out by the team of prof. Franco Locatelli del Bambino Gesù, has some advantages compared to the cells produced by the factories of the companies and then sent back frozen ”. Often, in fact, explains De Maria, the exact modification efficiency of the cells prepared by the companies is not known, which only provide an engineering range: “Instead, in our case, we know quite well how many cells have been modified, and this allows to inoculate a precise number of them in patients. Not only that: avoiding freezing and thawing reduces the stress to which these cells are subjected, theoretically also improving the effectiveness of the therapy “.
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The results on the first 3 children
The cells produced in this way and tested in the study involving the three children were very well tolerated and for now have produced complete remission: “After about two months, there is no sign of the disease,” says the expert. The study will continue in other patients with other strengths. “The aim, in addition to improving the effectiveness of the therapy, is also to make the process more sustainable, perhaps with agreements with the companies that hold the license for the technologies, without however totally entrusting the production to them”.
The Italian project
The Italian CAR-T project has another 5 work packages (WP), each of which addresses other problems related to CAR-T through the work of the various centers, mainly IRCCS of the Alliance Against Cancer Network (ACC). Purpose: the study of CAR-T at 360 °, within trials or on patients treated with already approved therapies, in order to increase its effectiveness and reduce toxicity. “For example – explains the president of ACC – WP2 is responsible for identifying new targets expressed by tumor cells that may be compatible with CAR-T therapy also for solid tumors”. WP3 conceptually follows WP2, aiming to test and develop new CAR-T on preclinical models, perhaps also through the use of cells other than T lymphocytes, such as NK cells. WP4, on the other hand, aims to identify and validate new strategies to reduce toxicity and above all to increase the effectiveness of these therapies, for example by trying to recruit components of the immune system independent of CAR-T that help fight cancer, resistant to the mechanisms of control and defense of our body. Finally, in WP5, the focus is on improving the safety profile of treatments, addressing the well-known problems of therapies, such as cytokine release syndrome or neurotoxicity problems. “All the different themes addressed by the project – concludes de Maria – will produce new knowledge and new applications in the field, for which it will also be necessary to address the legal aspects of intellectual property: the topic at the heart of WP6”.
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