A new form of tumor infiltrating lymphocyte (TIL) therapy showed promising results in the treatment of metastatic gastrointestinal cancers, according to a clinical trial led by the National Institutes of Health (NIH). The study, detailed in Nature Medicine on April 1, 2025, indicates that this immunotherapy could extend treatment options for various solid tumors.
TIL therapy involves selecting immune cells from tumors that target a patient's tumor cells, growing them in large quantities, and administering them back to the patient. In this trial, patients with various gastrointestinal cancers were additionally treated with the immune checkpoint inhibitor pembrolizumab (Keytruda) to boost immune responses. The combination resulted in significant tumor size reductions in 24% of patients, compared to 7.7% for those who received TILs alone. Patients receiving TILs unselected for anti-tumor activity did not experience tumor shrinkage.
"We're seeing the first extension of cellular therapy with TILs into the common solid cancers," noted Dr. Steven A. Rosenberg, the study's lead investigator. He added, "We see a little crack in the solid wall of cancer by using cell-based immunotherapy for the common solid cancers, and we think we have ways to open that crack even further."
The trial included 91 patients with cancers such as esophageal, stomach, pancreatic, colon, and rectal. These participants had previously undergone a median of four treatment regimens without success. In the trial's first phase, 18 patients received TILs not selected for anti-tumor activity, resulting in no objective responses. In subsequent phases, out of 39 patients receiving selected TIL therapy, 7.7% had objective responses. In the last phase, 34 patients treated with pembrolizumab before TIL therapy experienced the most significant results, with a 23.5% objective response rate.
Objective responses were observed in several cancer types, with responses lasting from several months to over five years. However, 30% of patients treated with selected TILs experienced serious side effects.
Efforts are underway to identify TILs that recognize specific neoantigens in tumors, potentially increasing the number of responsive patients. TIL therapy, first developed in the late 1980s by Dr. Rosenberg, was FDA-approved last year as lifileucel (Amtagvi) for advanced melanoma.
The trial was co-led by Dr. Rosenberg, Frank J. Lowery, Ph.D., and Stephanie L. Goff, M.D. from NCI. NCI, part of NIH, leads efforts to reduce cancer prevalence and improve patient outcomes through research and clinical training. NIH is the primary federal agency for medical research, addressing causes, treatments, and cures for various diseases.
