Genetically modified herpes combats advanced cancers

A new genetically engineered virus has delivered a one-two punch in initial phase 1 trial

Researchers have found that RP2 – a modified version of the herpes simplex virus – has 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 tried other treatments, including 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.

A team at The Institute of Cancer Research (ICR) London and The Royal Marsden NHS Foundation Trust, assessed the cancer-killing virus on its own in nine patients and in combination with the immunotherapy nivolumab in an initial 30 patients in the ongoing phase 1 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 – releasing the brakes on the immune system and increasing its ability to kill cancer cells.

Three out of nine patients treated with RP2 on its own benefitted from the treatment and 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 – a rare type of eye cancer – that had spread to the liver. They saw their cancers shrink and were still responding 18 and 15 months after starting treatment, respectively – meaning their cancer had not progressed.

Seven out of 30 patients who received both RP2 and the immunotherapy nivolumab also benefitted from treatment.

Study lead, Professor Kevin Harrington, Professor of Biological Cancer Therapies at The ICR, London, explained: “It is rare to see such good response rates in early-stage clinical trials, as their primary aim is to test treatment safety and they involve patients with very advanced cancers for whom current treatments have stopped working.

“Our initial trial findings suggest that a genetically engineered form of the herpes virus could potentially become a new treatment option for some patients with advanced cancers – including those who haven’t responded to other forms of immunotherapy. I am keen to see if we continue to see benefits as we treat increased numbers of patients.”

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