Researchers successfully exploit virus against advanced cancers

Herpes virus cells

A new genetically engineered herpes virus has delivered a one-two punch against advanced cancers in initial findings from a Phase I trial.

Researchers have found that RP2 – a modified version of the herpes simplex virus – showed signs of effectiveness in a quarter of patients with a range of advanced cancers.

Patients on the trial had cancers including skin, oesophageal and head and neck cancer and had exhausted other treatments, including by failing to respond to checkpoint inhibitor immunotherapy.

The early findings – presented at the 2022 European Society for Medical Oncology Congress (ESMO) – suggest cancer-killing viruses could potentially offer hope to some patients where other forms of immunotherapy have not worked.

Bursts cancer cells from within

A team at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, assessed the virus on its own in nine patients and in combination with the immunotherapy nivolumab in an initial 30 patients in the ongoing Phase I trial.

The early-stage study, sponsored by the drug’s manufacturer Replimune, is testing the safety and dosage of RP2, as well as evaluating its ability to shrink tumours.

The genetically engineered RP2 virus, which is injected directly into the tumours, is designed to have a dual action against tumours. It multiplies inside cancer cells to burst them from within, and it also blocks a protein known as CTLA-4 – increasing the immune system’s ability to kill cancer cells.

RP2 has also been modified to produce molecules called GM-CSF and GALV-GP-R, which give the virus additional capabilities to spark the immune system into action against cancer.

Promising initial findings

Three out of nine patients treated with RP2 alone saw their tumours shrink. One patient with salivary gland cancer saw his tumour disappear completely and remains free of cancer 15 months after starting treatment.

The other two patients in this group had oesophageal cancer and uveal melanoma that had spread to the liver. They saw their cancers shrink and were still responding 18 and 15 months after starting treatment, respectively.

Seven out of 30 patients who received both RP2 and nivolumab also benefitted from treatment. Of these, six remained progression-free at 14 months.

RP2 injections led to more immune cells in the area, including CD8+ T-cells, and ‘switched on’ genes linked to the ‘anti-cancer’ immune response.

Professor Kristian Helin, Chief Executive of The Institute of Cancer Research, London, said: “Viruses are one of humanity’s oldest enemies, as we have all seen over the pandemic. But our new research suggests we can exploit some of the features that make them challenging adversaries to infect and kill cancer cells. It’s a small study but the initial findings are promising. I very much hope that as this research expands we see patients continue to benefit.”

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