Scientists may be able to turn a longtime germline enemy into an ally in the fight against cancer, new research suggests this week. In preliminary data from a Phase I trial, a genetically modified version of the herpes virus has shown promise in treating hard-to-eradicate tumors, with one patient experiencing complete remission for 15 months so far. However, much more research will be needed to confirm the early success of the treatment.
The viral treatment is known as RP2 and is a genetically modified strain of herpes simplex 1, the virus responsible for most cases of oral herpes in humans, as well as some cases of genital herpes. Developed by the company Replimune, RP2 is designed work on two fronts. Injected directly into the tumor, the virus is supposed to selectively infect and kill certain cancer cells. But it also blocks the expression of a protein known as CTLA-4 produced by these cells and hijacks their machinery to produce another molecule called GM-CSF. The net result of these cellular changes is to weaken the cancer’s ability to hide and defend itself from the immune system.
In a Phase I trial conducted by scientists at the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust in the UK, RP2 was given as sole treatment to nine patients with advanced cancers that had not responded to other therapies ; it was also given in combination with another immunotherapy drug in 30 patients. Three patients with RP2 alone appeared to respond to the treatment, meaning their cancers either shrunk or stopped growing, and seven patients with the combination therapy also responded. One patient in particular, with a form of carcinoma along his salivary gland, has shown no signs of cancer for at least 15 months after treatment with RP2 alone. There were no life-threatening adverse events in the trial, and the most common symptoms after treatment were fever, chills and other flu-like illnesses.
The findings, presented This week at the European Society of Medical Oncology (ESMO) 2022 Congress, they are preliminary as they have not yet been approved through the formal peer review process. They are also based on a very small sample size, meaning any results should be taken with caution. But phase I trials aren’t meant to prove that a treatment is effective, only that it’s safe enough for humans to take. So the fact that some people with seemingly incurable cancers already seem to be responding to RP2, the team argues, is a very good sign that it may be living up to its potential.
“Our study shows that a genetically modified, cancer-killing virus can deliver a two-hit attack against tumors, directly destroying cancer cells from the inside while calling out the immune system against them,” said lead author Kevin Harrington, professor of biological cancer. Therapies at the Cancer Research Institute, a statement of the organization
Scientists have been hopeful about viruses that fight cancer for a long time. But only recently has this hope begun to bear fruit. 2015 was the first viral therapy approved in the US for certain advanced cases of melanoma. This May, scientists in California launched a phase I clinical trial of their anti-cancer virus, called Vaccination. others companies are developing their own candidates, either alone or in combination with other treatments. And Replimune is developing two other candidates based on its modified herpes virus.
Although many experimental therapies ultimately fail to cross the finish line and reach the public, it is possible that at least some of these viruses will one day become a new standard cancer treatment.