TIL Therapy: Cancer Immunotherapy Explained
TIL therapy is an innovative cancer immunotherapy in which tumor-infiltrating lymphocytes are harvested from a patient, expanded in the lab, and reinfused to fight cancer.
Things worth knowing about "TIL Therapy"
TIL therapy is an innovative cancer immunotherapy in which tumor-infiltrating lymphocytes are harvested from a patient, expanded in the lab, and reinfused to fight cancer.
What is TIL Therapy?
TIL therapy (Tumor-Infiltrating Lymphocyte therapy) is a form of adoptive cell therapy and one of the most promising advances in cancer immunotherapy. In this treatment, specialized immune cells called tumor-infiltrating lymphocytes (TILs) are extracted directly from a patient's tumor tissue, expanded to large numbers in the laboratory, and then infused back into the patient. The goal is to harness the immune system's own cancer-fighting cells and dramatically amplify their ability to recognize and destroy cancer cells.
Mechanism of Action
Tumor-infiltrating lymphocytes are T cells that naturally migrate into tumor tissue and attempt to attack cancer cells. However, within the tumor microenvironment, they are often present in insufficient numbers or suppressed by the tumor. TIL therapy overcomes this through the following steps:
- Harvesting: TIL cells are collected from resected tumor tissue, typically via surgical biopsy.
- Expansion: The isolated cells are grown in the laboratory using growth factors such as Interleukin-2 (IL-2), multiplying them into billions of cells.
- Lymphodepletion: Before the cells are returned, the patient receives a preparatory chemotherapy regimen (lymphodepletion) to create space and a favorable environment for the incoming TIL cells.
- Infusion: The expanded TIL cells are administered back to the patient via intravenous infusion.
- Supportive therapy: High-dose IL-2 is often given after infusion to support the survival and activity of the TIL cells in the body.
Indications and Applications
TIL therapy was originally developed and studied for metastatic melanoma (advanced skin cancer). Research has since expanded to other cancer types, including:
- Cervical cancer
- Non-small cell lung cancer (NSCLC)
- Breast cancer
- Other solid tumors
In 2024, the TIL product lifileucel (Amtagvi™) became the first TIL-based therapy to receive approval from the U.S. Food and Drug Administration (FDA) for previously treated unresectable or metastatic melanoma.
Advantages and Distinctive Features
A key advantage of TIL therapy over other cell-based immunotherapies (such as CAR-T cell therapy) is that TIL cells can recognize a broad range of tumor antigens, since they originate directly from the tumor. This makes them particularly valuable for tumors with high genetic variability and heterogeneity.
Side Effects and Risks
TIL therapy is an intensive treatment and can cause significant side effects, including:
- Side effects from lymphodepletion chemotherapy: fatigue, increased susceptibility to infections, nausea
- Side effects from IL-2 administration: fever, low blood pressure, fluid retention (edema), organ stress
- General immune reactions: inflammation, fever, chills
- Rarely: life-threatening systemic reactions
For these reasons, TIL therapy is administered exclusively in specialized oncology centers with close medical supervision.
Current Research and Outlook
TIL therapy is a rapidly evolving field. Numerous clinical trials are investigating its use in additional cancer types, as well as combination approaches with immune checkpoint inhibitors (e.g., PD-1/PD-L1 blockade) to further enhance efficacy. The development of genetically engineered TIL cells (engineered TILs) is also an area of intense scientific interest.
References
- Rosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer. Science. 2015;348(6230):62-68. doi:10.1126/science.aaa4967
- Rohaan MW, Wilgenhof S, Haanen JBAG. Adoptive cellular therapies: the current landscape. Virchows Archiv. 2019;474(4):449-461. doi:10.1007/s00428-018-2484-0
- U.S. Food and Drug Administration (FDA). FDA approves lifileucel for unresectable or metastatic melanoma. 2024. Available at: https://www.fda.gov
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