Tumor-infiltrating lymphocytes, or TILs, are immune T cells collected from a patient’s own tumor. Once isolated from the tumor sample, the TILs are tested in a specialized laboratory to find out which ones best recognize the patient’s tumor cells. Then, these selected lymphocytes are treated with substances that make them grow into the billions and are then infused back into the patient. The idea behind this approach is that the lymphocytes that are in or near the tumor are “pre-trained” to attack cancerous cells while leaving the healthy ones alone. But there may not be enough of them to kill the tumor or to overcome the signals that the tumor is releasing to suppress the immune system. Infusing large numbers of the lymphocytes that react best with the tumor can help to overcome these barriers.
Tumor-infiltrating lymphocyte (TIL) therapy was pioneered by Steven Rosenberg, M.D., and his colleagues in NCI’s Surgery Branch. In the late 1980s, Dr. Rosenberg led the first-ever clinical trials of TIL therapy, showing that it could shrink tumors in patients with metastatic melanoma.
There are two main types of T-cell transfer therapy (also called adoptive cell therapy, adoptive immunotherapy, and immune cell therapy): tumor-infiltrating lymphocytes (or TIL) therapy and CAR T-cell therapy. Both types involve collecting the patient own immune cells. But there’s a key difference between TILs and CAR T-cell therapies. For the approved CAR T-cell therapies (N1X10’s May 2023 blog article), the T cells are collected from a patient’s circulating blood. For TIL therapy, by contrast, the T cells are collected from the patient’s tumor.
With CAR T-cell therapy, the collected immune cells undergo genetic engineering (the gene for a special receptor called a chimeric antigen receptor -CAR- is inserted in the laboratory into the T cells genome) to give them the ability to recognize cancer cells and enhance their ability to kill them. Next, they are grown, or expanded, into the hundreds of millions, and then infused into the patient. With TIL therapy, once isolated from the tumor sample, the TILs are expanded (with the use of high-dose interleukin, IL-2) into the billions and infused back into the patient. In contrast to CAR T-cell therapy, TILs are not engineered before being expanded. That’s because, having been collected from samples of tumor tissue, they’ve already proven that they can recognize and navigate to tumors, Dr. Rosenberg explained.
A TIL Working Group, composed of an internationally recognized multidisciplinary team including surgeons, hematopoietic stem cell transplant physicians, and solid tumor oncologists with expertise in TIL cell therapy, has been established in collaboration with industry experts to aid healthcare practitioners in better understanding and administering TIL cell therapy.
On February 16, 2024, the Food and Drug Administration (FDA) announced the approval of lifileucel (Amtagvi), the first treatment for cancer that uses TILs for the treatment of a solid tumor – metastatic melanoma – that progressed after treatment with a PD-1/PD-L1-targeted immune checkpoint inhibitor or a BRAF inhibitor.
