TIL, a small acronym for what seems to be the next great frontier against cancer. We are talking about an approach that has been studied since the 1990s, but which has had a strong boost in the last decade, with experiments on different types of solid tumors. And now the Food and Drug Administration has just approved, with an accelerated procedure, the first TIL cell therapy, lifileucel, which can be used in patients with metastatic melanoma resistant to other treatments. Not only that: a new study on this new therapy will start in the coming months which will also involve Italian patients.

Breast cancer: the new challenge is to enlist the immune system

by Tiziana Moriconi


A ‘new’ type of immunotherapy

“TIL cell therapy is a type of immunotherapy, studied over 20 years ago by Steve Rosenberg, the pioneer of CAR-T therapies – he explains Paolo Ascierto, director of the Melanoma Oncology, Oncological Immunotherapy and Innovative Therapies Unit of the National Cancer Institute “G. Pascale” of Naples – It is what I define as ‘immunotherapy 4.0’: in fact we started with immune checkpoint inhibitor drugs that we have been using for over 10 years now, then CAR-T cell therapies arrived for some blood tumors, more recently mRNA vaccines (currently in the testing phase, ed.) and now TILs are arriving.”

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What is it about

Indeed, TIL cell therapies are at the center of the annual congress of the Campania Society of Oncological Immunotherapy (SCITO), underway in Naples. But what do they consist of, exactly? “TIL is the acronym for ‘Tumor Infiltrating Lymphocytes’, i.e. immune cells found inside solid tumors and which therefore have a high capacity to recognize them. The procedure consists in removing a part of the tumor mass, separating the T lymphocytes from it and placing them in culture in the laboratory to make them ‘multiply’, thanks to the use of an interleukin”. In fact, it is necessary to obtain an ‘army’ of billions of TIL cells capable of recognizing the tumor, a process that takes 4 to 6 weeks. “At that point – continues Ascierto – the TILs are reinfused into the patient, who in the meantime has undergone lymphodepletion, i.e. all the other lymphocytes have been eliminated. TILs are then encouraged to take their place, in the hope that they will improve disease control. Unlike CAR-T therapies, therefore, lymphocytes are not genetically modified, even if this is a possible evolution.”

Manipulating the immune system to defeat cancer

The approval in the USA and the new study in Italy

L’approval of lifileucel in the USA it was based on one phase 2 clinical trial led by Moffitt Cancer Center (in Florida, USA). To date, the results have shown an objective response in 36% of heavily pretreated patients with metastatic melanoma, and in 41% of these the response lasted for more than 18 months. “These are important data, which today give hope to those who have relapsed or have not benefited from other treatments – comments Ascierto – For these patients, he concludes, the phase 3 clinical study will start at the Pascale Cancer Institute in Naples by 2024 on lifileucel, to evaluate the safety and efficacy of therapy in combination with pembrolizumab, an inhibitor of the PD1/PD-L1 immune checkpoint, compared with treatment with pembrolizumab alone”.

Melanoma, good results for immunotherapy that infiltrates lymphocytes

by Fabio Di Todaro



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