Tumor infiltrating lymphocyte therapy treats cancer on a large scale

Tumor infiltrating lymphocyte therapy treats cancer on a large scale
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A novel treatment strategy using personalized cell therapy improves progression-free survival compared to standard immunotherapy in patients with advanced melanomaaccording to groundbreaking results reported at ESMO 2022 from the phase 3 M14TIL study.

“This study shows for the first time in a randomized controlled trial that cell therapy can be effective and beneficial for patients with solid cancers,” said lead author John Haanen, Netherlands Cancer Institute, Amsterdam, The Netherlands. “In melanoma patients, we see a 50 percent reduction in the likelihood that the disease will progress or die from the disease, which is absolutely practice changing. This is the first time a TIL-based approach has been directly linked to standard-of-care treatment, in this case ipilimumab. As a result, we can now position TIL treatment much better in the treatment landscape for patients with metastatic melanoma.”

“TIL therapy is an exceptional therapy,” commented George Coukos, University Hospital Lausanne and Ludwig Institute for Cancer Research, Lausanne, Switzerland, who was not involved in the study. “TIL is a new paradigm for the treatment of cancer and, as these results clearly demonstrate, it is effective and feasible at scale.

Treatment essentially involves taking a small sample from the resected tumor of a patient who becomes immune T cells from the tumor in the laboratory and then infuse the personalized TIL therapy back into the patient after chemotherapy. TILs recognize tumor cells as abnormal, invade them, and then work to kill them.

The phase 3 M14TIL study randomized 168 patients with unresectable stage IIIC-IV melanoma to receive immunotherapy with the anti-CTLA-4 antibody ipilimumab or TIL treatment; most patients had failed prior anti-PD-1 treatment. Results, first reported at ESMO 2022, showed that patients treated with TIL therapy had a significantly longer median progression-free survival of 7.2 months compared to 3.1 months in patients who received ipilimumab; the overall response rate to TILs was 49% versus 21% for ipilimumab; The median overall survival was 25.8 months versus 18.9 months. Patients will continue to be followed up for overall survival.

Treatment options for patients with metastatic melanoma have changed significantly over the past 10 years with the development of checkpoint inhibitors, including the PD-1 inhibitors nivolumab and pembrolizumab and the CTLA-4 inhibitor ipilimumab. These drugs release a natural brake on the immune system so that the body’s own defense cells can recognize and attack tumor cells. “They have a very good safety profile and are quite high effectiveness and are now often administered as first-line therapy. But when patients fail first-line therapy, options become very scarce, especially for patients who fail anti-PD-1 drugs, so there’s a real unmet need,” Haanen explained. He added, “In our study, 89% of patients failed anti-PD-1 treatment.” The remaining patients entered the study before anti-PD-1 therapies were approved.

Haanen investigated the possible mechanism by which TIL therapy is effective in patients who have failed anti-PD-1 treatment and suggested: “We believe that the mechanism of resistance to the anti-PD-1 -Treatment is mainly delivered by the tumor microenvironment. So when we take these cells from their natural environment, reactivate them in the lab, grow them into very large numbers and give them back to patients, we can overcome some of the escape mechanisms. And that’s what we see – otherwise TILs”tt would work in this environment.”

Although all patients treated with TIL therapy and 57% of patients who received ipilimumab experienced grade 3 or higher adverse events, Haanen specified: “The side effects are well manageable and mostly resolve when the patients do so Leaving the hospital after their TIL therapy”. He added that most side effects are related to other therapies, including chemotherapy and interleukin-2, that patients receive as part of the TIL regimen. On the effects of TIL therapy, Haanen concluded: ” TIL has the potential to help patients with a variety of solid tumors, and trials are ongoing in many types of cancer, including lung, cervical, and head and neck cancer.”

Haanen explained that the study was carried out by academics in the Netherlands and Denmark without industry involvement. Researchers are now working to get EMA approval for their TIL therapy to ensure it remains affordable and free from commercial pressures.

“The results of this phase 3 study could potentially lead to regulatory approval that would change the practice,” Coukos said. “It would allow countries considering this avenue to establish centers that can offer TIL therapies to patients and establish this as a potential second-line treatment for advanced melanoma.”

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