Genetically Modified Herpes Virus Kills Two Birds With One Stone in Cancer

Early findings from a phase-I clinical trial using a new genetically modified virus prompted the comment that, in advanced cancers, “two birds were killed with one stone.”

Researchers found that a modified version of the cold sore virus, herpes simplex, called RP2, was effective in a quarter of patients with a range of advanced cancers.

Patients in this early-stage trial had cancers including skin, esophageal, and head and neck cancer, and had exhausted other treatment options, including a lack of response to checkpoint inhibitor immunotherapy.

At the 2022 European Society for Medical Oncology (ESMO) Congress, this study was presented, suggesting that oncolytic (cancer-killing) viruses may potentially offer hope to some patients for whom other forms of immunotherapy have not worked.

The mechanism of action of an oncolytic virus vaccine is illustrated simply below:

RP2 Safety, Dosing and Efficacy Data

In an ongoing phase I trial, a team from the Institute of Cancer Research in London and The Royal Marsden NHS Foundation Trust administered the cancer-killing virus alone to 9 patients and to the first 30 patients with the immunotherapy nivolumab as combination treatment.

The early-stage study, sponsored by the medicine's manufacturer Replimune, tested RP2 safety and dosing and assessed its ability to shrink tumors.

The genetically modified RP2 virus, injected directly into tumors, is designed to have a dual effect against tumors:

1. The virus multiplies inside cancer cells to burst them from within, and
2. It also blocks a protein known as CTLA-4, releasing the brakes on the immune system and increasing its ability to kill cancer cells.

RP2 has also been modified to produce molecules called GM-CSF and GALV-GP-R, giving the virus additional abilities to activate the immune system against cancer.

10 Patients Benefited From RP2

Three of the nine patients treated with RP2 benefited from treatment and saw their tumors shrink. One patient with advanced salivary gland cancer saw their tumor disappear completely and remained cancer-free 15 months after starting treatment.

The other two patients in this group had esophageal cancer that had spread to the liver and a rare eye cancer called uveal melanoma. Their cancers shrank, and they were still responding 18 and 15 months after starting treatment, meaning their cancers had not progressed.

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

In this group, four of nine patients with melanoma skin cancer, two of eight patients with uveal melanoma eye cancer, and one of three patients with head and neck cancer saw their cancers stop growing or shrink.

Six of the seven patients who received and benefited from the combination had no cancer progression for 14 months.

All study participants had advanced cancers and had exhausted standard treatment options or were unsuitable for them.

Triggering an Immune Response Against Cancer

Researchers examined patient biopsies before and after RP2 injections and found positive changes in the tumor immune microenvironment, the area immediately around the tumor. The injections led to more immune cells in the area, including CD8+ T cells, and activated genes associated with an “anticancer” immune response.

Researchers found that most RP2 side effects were mild; fever, chills and fatigue were among the most common. None were serious enough to require medical intervention.

The researchers next hope to continue exploring RP2's potential in more patients.

RP2: Killing Two Birds With One Stone Against Tumors

This study shows that a genetically modified, cancer-killing virus can kill two birds with one stone against tumors: directly destroying cancer cells from within while activating the immune system against them.

It is rare to see such good response rates in early-stage clinical trials because their primary aim is to test treatment safety and they include patients with very advanced cancer for whom existing treatments no longer work.

The findings suggest that a genetically modified form of herpes virus could potentially provide a new treatment option for some patients with advanced cancer, including those who have not responded to other forms of immunotherapy. Whether this benefit continues in phase II-III studies involving more patients remains an open question.

Using Viruses in Cancer Treatment

As we all saw during the pandemic, viruses are among humanity's oldest enemies. Yet this new research shows that we can exploit some of their characteristics to infect and kill cancer cells. This is a small study, but the initial findings are promising. We hope to see patients continue to benefit as the research expands.

One Patient's Story

Krzysztof Wojkowski, a 39-year-old builder from West London, was diagnosed with mucoepidermoid carcinoma, a type of salivary gland cancer, in May 2017. After many operations, he was told there were no treatment options left before being offered the opportunity to join this oncolytic virus therapy study. He describes his experience as follows:

“I was told there were no options left for me, and I was receiving end-of-life care. It was devastating, so being offered the chance to join this human trial at The Royal Marsden was incredible. It was my last lifeline. I received injections every two weeks for five weeks, and they completely eliminated my cancer. I have lived without signs of cancer for two years. It is a real miracle; there is no other word to describe it. I have been able to work as a builder again and spend time with my family. There is nothing I cannot do.”