An Overview of TIL Therapy
An expert in the management of non–small cell lung cancer defines tumor-infiltrating lymphocyte (TIL) therapy by discussing its mechanism of action and reviewing its impact in other disease states, such as myeloma.
Adam J. Schoenfeld, MD: TIL [tumor-infiltrating lymphocyte] therapy is a long way of saying we’re using the power of someone’s own immune cells that have already identified and invaded the tumor. The process involves the identification and isolation of these immune cells from a tumor after a surgery. It may end up being a biopsy in the near future. Then the cells are expanded outside of the body to create a large number of them that can be reinfused back into a patient, where they can seek out and destroy remaining tumor cells anywhere throughout the body. The treatment involves multiple steps. It involves a tumor resection initially so you can identify and extract the immune cells. Then it involves treatment with chemotherapy prior to the treatment with the TILs to make space for the TILs to grow and expand in the body. That is followed by the TIL therapy and an immune-boosting therapy called IL-2 to help the TILs grow throughout the body and target the cancer cells.
The mechanism of action of TIL therapy has to do with exploiting your own immune recognition of tumor cells. By taking out the tumor and identifying and isolating the immune cells within the tumor, we have already identified cells that can recognize the tumor cells. This could be multiple clones or populations of immune cells, or a single clone that targets multiple types of tumor cells.
TIL therapy gets lumped in with CAR [chimeric antigen receptor] and TCR [T-cell receptor] therapy, but it is quite different. Those other types of cell therapies are reengineering or reprogramming cells to target specific proteins or other molecules related to cancer cells. TIL therapy uses your own native immune system that has already identified the tumor cells, expands that population of cells, and then creates space for it to be reinfused and potentially effective in a more supportive environment throughout your body.
The concept of TIL therapy is not new. It was pioneered at the National Cancer Institute decades ago by Steven Rosenberg, [MD, PhD,] and multiple colleagues. However, the technology has evolved to enable this type of therapy to be used throughout a number of tumor types and be more effective in a much larger patient population. The process and window for manufacturing has shortened considerably. You can now generate a larger TIL product with far fewer tumor cells. In melanoma, where TIL has had the most experience, it has shown to be effective and tolerable after progression on immunotherapy, and may soon receive regulatory approval. In lung cancer, early phase trials are ongoing, but I hope we will see similar findings.
TIL therapy was first used primarily in melanoma. It was used prior to the advent of other immunotherapies, like checkpoint blockade. More recently, there have been larger clinical trials that have investigated whether TIL therapy can be used more broadly in melanoma after patients have progressed on treatment with checkpoint blockade. The findings have been quite striking. There has been about a 36% response rate among patients who are resistant to other immunotherapies. These responses can be durable, lasting months to years in some patients. That’s after just 1 infusion of TIL therapy and monitoring the patient over a longer period.
Transcript edited for clarity.
