Breakthrough study by ICR reveals potential life-saving combination of oncolytic virus and ILP for sarcoma and melanoma patients

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(IN BRIEF) Researchers at The Institute of Cancer Research, London, have achieved a breakthrough in the treatment of advanced sarcoma and melanoma through a novel combination of isolated limb perfusion (ILP) and oncolytic virus therapy. In the first clinical trial of its kind, patients received the virus T-VEC prior to ILP, resulting in both local and systemic immune activation against tumours. The therapy demonstrated a 53 percent overall response rate, with several patients remaining disease-free for years and showing strong immune activation across the body. Beyond preserving limbs that might otherwise require amputation, this treatment could pave the way for new immunotherapy-based strategies to manage metastatic cancer. Supported by NIHR, The Royal Marsden, and Sarcoma UK, the research highlights how combining regional and systemic therapies may revolutionize treatment for immunotherapy-resistant cancers.

(PRESS RELEASE) LONDON, 7-Nov-2025 — /EuropaWire/ — The Institute of Cancer Research (ICR), London, has announced groundbreaking clinical findings that may redefine treatment options for patients suffering from advanced sarcoma and melanoma affecting their limbs. In a pioneering trial, researchers successfully combined an existing cancer-fighting virus therapy with isolated limb perfusion (ILP), a targeted chemotherapy technique, revealing the potential to trigger both local and systemic immune responses against the disease.

The approach involved administering the oncolytic virus talimogene laherparepvec (T-VEC) prior to ILP treatment, allowing doctors to not only treat tumours directly within the affected limb but also stimulate the body’s immune system to combat cancer cells throughout the body. This promising combination could make tumours more receptive to immunotherapy, offering new hope for patients whose disease is too advanced for surgical removal and may otherwise require amputation.

ILP enables the delivery of high-dose chemotherapy directly to a limb while temporarily isolating its blood circulation, thus sparing the rest of the body from toxic exposure. However, while effective in destroying tumours locally, ILP typically does not influence cancer cells that have already spread elsewhere. The integration of T-VEC—a genetically modified herpes simplex virus that infects and kills cancer cells while simultaneously activating the immune system—could change that dynamic.

In this first-in-human phase I/II trial, 15 patients with sarcoma or melanoma received T-VEC injections into their tumours before undergoing ILP. The treatment was well tolerated, with mainly mild to moderate side effects, and achieved an overall response rate of 53 percent. Remarkably, some patients remained disease-free for up to three years, and several sarcoma cases—traditionally resistant to both ILP and immunotherapy—showed sustained responses.

Detailed analysis of tumour and blood samples revealed that the therapy enhanced the expression of immune-related genes, particularly in patients who responded best. The researchers also observed increased diversity in T-cell receptors, indicating a robust systemic immune activation beyond the treated limb. These findings suggest that while ILP is a localized procedure, its combination with T-VEC may provide broader protection against metastasis.

Preclinical studies support the potential for even stronger outcomes. In laboratory models, delivering T-VEC as part of the ILP circuit enabled significantly higher concentrations of the virus to penetrate the tumour core. Although current licensing limitations restricted such delivery during this human trial, researchers believe future studies could optimize dosing and timing—and potentially combine the treatment with immunotherapy agents to further suppress secondary tumour formation.

Professor Andrew Hayes, Consultant Surgeon and Oncologist at The Royal Marsden and Honorary Faculty at ICR, described the results as “potentially transformative” for patients facing limited options. “This could be a game-changer,” he said. “We’ve demonstrated that viral therapy can enhance both local and systemic immune control, giving new hope to sarcoma patients at high risk of metastasis.”

Senior author Professor Alan Melcher, who leads the Translational Immunotherapy Group at ICR, added: “Delivering oncolytic virotherapy through isolated limb perfusion has shown it can turn immunologically cold tumours into hot ones. Our next step is to refine this approach—adjusting doses, timing, and immunotherapy combinations—to fully harness its potential for patients whose cancers have been resistant to existing treatments.”

Funded by the NIHR Biomedical Research Centre at ICR and The Royal Marsden NHS Foundation Trust, along with Sarcoma UK, Amgen Pharmaceuticals, and several charitable foundations, the study marks a significant milestone in efforts to expand the benefits of immunotherapy to more patients with advanced solid tumours.

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SOURCE: The Institute of Cancer Research