Generation of TIL-based Cellular Products for Cancer Immunotherapy: Current Insights and the Challenges

Tumor-infiltrating T lymphocytes (TILs) are a population of T cells present in tumor tissue and enriched in tumor antigen-specific clones. TILs participate in the adaptive antitumor immune response, which makes them a promising candidate for cancer immunotherapy. The concept framing this type of therapy involves the extraction of T cells from a patient's tumor, followed by their in vitro expansion and reinfusion into the same patient in large quantities. This approach enhances the antitumor immune response and allows one to affect cancer cells resistant to other types of treatment. In 2024, the first TIL-based drug was approved for melanoma treatment. The possibility of using TILs for treating other solid tumors is currently being considered, and novel methods aiming to increase the efficiency of generating TIL cultures from tumor tissues in vitro are being developed. However, despite the significant progress achieved in this area, there remain unresolved issues and problems, including the lack of standardized protocols for obtaining, expanding, and cryopreserving TILs, the complexity related to their isolation and the duration of that, as well as insufficient efficiency. Our review focuses on the concept of immunotherapy using TILs, the main stages involved in generating a TIL-based cellular product, associated problems, and further steps in the production of TIL cultures that aim to improve efficiency as relates to production and ensure a wider application of the therapy.