New Cell Therapy Shows Promise for Hard-to-Treat Gastrointestinal Cancers

A new approach to immunotherapy has shown promising results in shrinking a variety of metastatic gastrointestinal cancers, marking a breakthrough for cell-based treatments targeting solid tumors. Researchers from the National Institutes of Health (NIH) reported that combining a refined form of tumor-infiltrating lymphocyte (TIL) therapy with an immune checkpoint inhibitor led to significant tumor reduction in patients with advanced-stage colon, rectal, pancreatic, and bile duct cancers.

The trial, led by the NIH’s National Cancer Institute, included 91 patients whose cancers had progressed despite undergoing a median of four previous treatment regimens. In its most effective form, the treatment involved selecting TILs with strong tumor-targeting properties, expanding them in a lab, and then infusing them back into the patient. When combined with pembrolizumab (Keytruda), an immune checkpoint inhibitor, the therapy resulted in tumor shrinkage in 23.5% of patients—a marked improvement over the 7.7% response seen in those who received the selected TILs without pembrolizumab. Patients treated with unselected TILs saw no tumor reduction.

Objective responses—defined as tumor shrinkage of at least 30%—were observed across several types of gastrointestinal cancers in the later phases of the trial. Tumor responses lasted from several months to nearly six years in some cases. Serious side effects were reported in about 30% of patients receiving the selected TILs, a figure consistent with other intensive immunotherapies. Researchers are now working to refine the selection process for TILs by targeting tumor-specific proteins known as neoantigens, aiming to broaden the range of patients who could benefit from the therapy.

The trial builds on decades of research into TIL therapy, which was first developed at NIH in the late 1980s. In 2023, the FDA approved the first TIL therapy for solid tumors, lifileucel (Amtagvi), for advanced melanoma. The new findings extend the potential of this approach to more common and harder-to-treat cancers.

Article by multiple RFHC contributors, based upon information from the National Institutes of Health press release

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