TIL, a small acronym for what appears to be the next big challenge in the fight against cancer. We are talking about an approach that has been studied since the 1990s, but which has seen a major boost in the last decade through experiments on different types of solid tumors. And now the Food and Drug Administration just approved, with an accelerated process, the first TIL cell therapy, lifileucel, that can be used in patients with metastatic melanoma who are resistant to other treatments. In addition, a new study of this new therapy will begin in the coming months, which will also involve Italian patients.

Breast cancer: The new challenge is to activate the immune system

by Tiziana Moriconi

A “new” type of immunotherapy

“TIL cell therapy is a type of immunotherapy that was studied over 20 years ago by Steve Rosenberg, the pioneer of CAR-T therapies,” he explains Paolo Ascierto, Director of the Division of Melanoma Oncology, Oncological Immunotherapy and Innovative Therapies of the National Cancer Institute “G. Pascale” from Naples – This is what I define as “Immunotherapy 4.0”: In fact, we started with immune checkpoint inhibitor drugs, which we have been using for over 10 years now, and then more recently came CAR-T- “Cell therapies for some blood tumors are coming onto the market, mRNA vaccines (currently in the test phase, editor’s note) and now TILs are coming.”

The therapeutic vaccine against melanoma reduces the risk of metastasis

by Letizia Gabaglio

What is it about

In fact, TIL cell therapies are the focus of the annual congress of the Campania Society of Oncological Immunotherapy (SCITO), currently taking place in Naples. But what exactly are they made of? “TIL is the abbreviation for ‘Tumor Infiltrating Lymphocytes’, ie immune cells that occur in solid tumors and therefore have a high ability to recognize them. The procedure consists in removing part of the tumor mass, separating the T lymphocytes from it and putting them in culture in the laboratory so that they “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 this point,” Ascierto continues, “the TILs are reinfused into the patient, who has now suffered lymphodepletion, meaning all other lymphocytes have been eliminated.” TILs are then encouraged to take their place in the hope that they will provide disease control improve. Therefore, unlike CAR-T therapies, lymphocytes are not genetically modified, although 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 lead by Moffitt Cancer Center (in Florida, USA). So far, results have shown objective responses in 36% of heavily pretreated patients with metastatic melanoma, and in 41% of these, responses were sustained for longer than 18 months. “These are important data that today give hope to those who have suffered a relapse or who have not benefited from other treatments,” comments Ascierto. “For these patients, he concludes, the Phase 3 clinical trial will begin by 2024 at the Pascale Cancer Institute in Naples.” Lifileucel, to test the safety and effectiveness of the therapy in combination with pembrolizumab, an inhibitor of PD1/ PD-L1 immune checkpoints, compared to treatment with pembrolizumab alone.”

Melanoma, good results for immunotherapy that infiltrates lymphocytes

by Fabio Di Todaro