CAR-T therapy is one of the most revolutionary approaches of these years, but Tumor-infiltrating lymphocytes (TILs) are taking the stage for the treatment of solid tumor
Immunotherapy is considered a novel and revolutionary approach for the treatment of tumors. Many types of Immunotherapies have been developed to help patients’ immune system fighting against tumors by blocking immune checkpoints, or providing monoclonal antibodies, vaccination and finally with the transfection of mature T cells that directly recognize a specific tumoral antigen. In this scenario, the Chimeric Antigen Receptor T (CAR-T) therapy is one of the most revolutionary approaches based on T cells transfection and till the 16th of February 2024 was the sole immune cell based therapy approved by the world drug authorities. But now the Tumor-infiltrating lymphocytes (TILs) are taking the stage for the treatment of solid tumor.
CAR-T and TILs therapy: similarities and differences
The CAR-T therapy involves the transfection of modified T cells from a patient to enhance their ability to detect and destroy tumor cells. While promising, this approach is primarily effective against circulating tumors, but it is less suitable for solid tumors that are challenging to be targeted due to the absence of circulating cells and the presence of an immunosuppressive microenvironment.
TILs therapy originated in the late 1980s through a clinical trial initiated by Dr. Rosenberg. Similar to CAR-T therapy, TILs therapy involves collecting T cells from patients and reintroducing them into the patient. However, there is a crucial difference in the source of cells between these two approaches. While CAR-T therapy relies on circulating T cells that are collected and engineered, TILs therapy uses T cells isolated from the tumor microenvironment. Due to this distinction, while CAR-T cells require genetic modification to insert a chimeric antigen receptor, enabling selective targeting of tumor cells, TILs do not require genetic modification as they naturally express receptors necessary for selective infiltration into tumors.
FDA approval: using tumor-infiltrating lymphocytes (TILs) for solid cancer treatment
Recently, a groundbreaking milestone was achieved in immunotherapy with the approval by the Food and Drug Administration (FDA) of the first cell-based immunotherapy targeting solid tumors. Prior to February 16th, six CAR-T therapies were available, but now the Lifileucel (Amtagvi) has received FDA approval, marking it the first use of tumor-infiltrating lymphocytes (TILs) for solid cancer treatment. This approval is particularly significant for patients who are resistant to conventional immunotherapies for melanoma skin cancer. The authorization is based on the results of several National Clinical Trial (NCT), NCT02360579, NCT03083873, NCT03108495, NCT03645928, and NCT04614103. Despite this accelerated approval the full authorization underlies to the results of a phase III clinical trial (IOV – MEL-301) that will investigate the efficacy of Lifileucel on 670 participants from 2023 to 2030.
Given to this difference TILs therapy, as showed in a published phase II study (https://jitc.bmj.com/content/10/12/e005755), reduce the risk of a common side effect of CAR-T therapy, the cytokine release syndrome, highlighting this approach as a revolutionary therapy for solid tumor.
By Lorenzo Da Dalt Department of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”, University of Milan
Link: https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/amtagvi