How tumor-infiltrating lymphocyte therapy is made from your own tumor, who may be a candidate, what the hospital stay involves, and what the evidence shows.
Some immune cells find their way into a melanoma on their own. These tumor-infiltrating lymphocytes, or TILs, are T cells that already recognize the cancer. Inside the tumor they are outnumbered and worn down. TIL therapy removes them, grows them into the billions in a laboratory, and returns them to the patient as a single infusion.
The cells are not genetically engineered, which sets TIL therapy apart from CAR T-cell therapy used in blood cancers. A commercial version, lifileucel (Amtagvi), is now available at authorized treatment centers in the United States.
The FDA granted accelerated approval to lifileucel on February 16, 2024. The National Cancer Institute described it as the first cellular therapy approved for a solid tumor. The approval covers adults with melanoma that cannot be removed by surgery or has spread, and that was previously treated with a PD-1 blocking antibody. If the melanoma has a BRAF V600 mutation, the person must also have received a BRAF inhibitor, with or without a MEK inhibitor.
In plain terms, TIL therapy is a later-line option. Accelerated approval means the FDA acted on early evidence of tumor shrinkage and requires further study to confirm the benefit.
The chemotherapy, infusion, and IL-2 together span about a week and a half, and recovery adds more time. IL-2 and lifileucel are usually given in the hospital, according to the American Cancer Society. Centers often ask patients to stay nearby for a period after discharge.
A person needs at least 1 tumor that a surgeon can remove to supply the cells. The treatment is hard on the body, so centers look for good general health with sound heart, lung, and kidney function.
Timing matters as well. The melanoma keeps growing during the 5 weeks or so of manufacturing, and some people need another treatment to hold it in check while they wait. National Cancer Institute experts have noted that people with a large amount of cancer, or with spread to the brain or liver, appear less likely to respond.
Every participant in the lifileucel trial had side effects, and most came from the supporting drugs, not the cells. The chemotherapy drives blood counts very low for a time. Low white cells raise the risk of serious infection, low platelets raise the risk of bleeding, and low red cells cause anemia.
High-dose IL-2 causes high fevers, shaking chills, low blood pressure, fluid buildup, a fast heart rate, and shortness of breath. The effects are intense and short. Doctors stop IL-2 doses early when a patient has had enough. The National Cancer Institute reports that most side effects occur in the first 2 to 3 weeks.
The risks are serious. Lifileucel carries an FDA boxed warning for treatment-related death, prolonged severe low blood counts, severe infection, and heart, lung, and kidney problems. The prescribing information lists a treatment-related death rate of 7.5% in the trial. For this reason the therapy is given only at centers with intensive care support and staff trained to manage IL-2.
The FDA approval rested on a single-arm trial, meaning every participant received lifileucel and no comparison group existed. Among 73 patients treated within the recommended dose range, all of whom had melanoma that had grown despite earlier treatment, 31.5% had their tumors shrink. That figure includes 3 complete responses, in which all visible cancer disappeared. Responses began at a median of 1.5 months, and the prescribing information reports that more than half of responders were still responding at 6 months.
A randomized trial supports the general approach. In a phase 3 study from the Netherlands and Denmark (Rohaan and colleagues, New England Journal of Medicine, 2022), 168 patients with advanced melanoma, 86% of whom had already failed PD-1 immunotherapy, received either TIL therapy made at the hospital or ipilimumab. Tumors shrank in 49% of the TIL group and 21% of the ipilimumab group. The median time before the melanoma grew again was 7.2 months with TILs and 3.1 months with ipilimumab.
That trial used TILs produced by academic laboratories, not lifileucel, so the results are not interchangeable. More data is needed on how long responses last and on whether TIL therapy helps people live longer.
