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Trial shows Combination Immunotherapy May be effective against Various Gastrointestinal Cancers - Video
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Overview
A new form of tumor infiltrating lymphocyte therapy, a form of personalized cancer immunotherapy, improved the treatment's effectiveness in patients with metastatic gastrointestinal cancers, according to results of a clinical trial published in Nature Medicine.
This therapy could be used to treat a variety of solid tumors, which has so far eluded researchers developing cell-based therapies.
This form of therapy involves identifying and selecting immune cells that are found in the tumor that specifically recognize and attack a patient’s tumor cells. Next, scientists grow those tumor infiltrating lymphocyte into large quantities in the laboratory before they are finally administered to the patient.
Patients in the clinical trial, who had a variety of gastrointestinal tumors, also received the immune checkpoint inhibitor pembrolizumab (Keytruda) to help further boost their immune response. The result was nearly 24% of patients treated with selected tumor infiltrating lymphocyte plus pembrolizumab had a substantial reduction in the size of their tumors, compared with 7.7% of patients who received selected tumor infiltrating lymphocyte without pembrolizumab. Patients treated with tumor infiltrating lymphocyte that had not been selected for anti-tumor activity had no tumor shrinkage.
The clinical trial included 91 patients with metastatic gastrointestinal cancers—including esophageal, stomach, pancreatic, colon, and rectal cancers—that had worsened despite a median of four prior treatment regimens. In the pilot phase of the trial, 18 patients were treated with tumor infiltrating lymphocyte that had not been selected for anti-tumor activity, and there were no objective responses. In the second phase, 39 patients were treated with selected tumor infiltrating lymphocyte therapy, and 7.7% had objective responses.
In the third phase, 34 patients received pembrolizumab immediately before selected tumor infiltrating lymphocyte therapy. This group had the best response, with 23.5% patients experiencing an objective response. All 91 patients had also received standard chemotherapy and high-dose interleukin-2 before the tumor infiltrating lymphocyte therapy.
In the trial’s second and third phases, objective responses were seen in multiple types of gastrointestinal cancers, including cancers of the colon, rectum, pancreas, and bile duct. Responses lasted between 8 months and more than 5.8 years in the group that received selected tumor infiltrating lymphocyte therapy alone, and between 4 months and 3.5 years in the group that received selected tumor infiltrating lymphocyte therapy and pembrolizumab. Serious side effects occurred in 30% of patients treated with selected tumor infiltrating lymphocyte.
Reference: Lowery, F.J., Goff, S.L., Gasmi, B. et al. Neoantigen-specific tumor-infiltrating lymphocytes in gastrointestinal cancers: a phase 2 trial. Nat Med (2025). https://doi.org/10.1038/s41591-025-03627-5
Speakers
Dr. Bhumika Maikhuri
BDS, MDS
Dr Bhumika Maikhuri is a Consultant Orthodontist at Sanjeevan Hospital, Delhi. She is also working as a Correspondent and a Medical Writer at Medical Dialogues. She completed her BDS from Dr D Y patil dental college and MDS from Kalinga institute of dental sciences. Apart from dentistry, she has a strong research and scientific writing acumen. At Medical Dialogues, She focusses on medical news, dental news, dental FAQ and medical writing etc.