One of the strategies of scientists to combat diseases that have no cure, or whose treatment is laborious or produces unwanted side effects, is to check if drugs already approved to treat other conditions are effective. Researchers also modify viruses in their labs into potential drugs, and one study has shown that a genetically modified herpes virus has been effective in a number of patients suffering from a variety of advanced cancers.
Initial results from a phase I trial revealed that RP2, a modified version of the herpes simplex virus, showed signs of efficacy in a quarter of patients who participated in the trial who had various types of cancer, including skin cancer, esophageal and head and neck cancers, and were no longer responding to other treatments, including immunotherapy with checkpoint inhibitors.
The study authors, a team from the London Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, have presented these early findings at the European Society for Medical Oncology (ESMO) Congress in 2022, suggesting that viruses that kill cancer could provide hope for some patients in whom other forms of immunotherapy have failed.
They tested the safety and efficacy of RP2 against cancer in 39 patients
In the ongoing phase I trial, researchers tested the cancer-killing virus in nine patients as a single therapy, and in 30 patients they administered it in combination with the immunotherapy nivolumab. This first stage of the trial has been sponsored by Replimune, the manufacturer of RP2, to test the safety of the drug and verify the necessary dose, as well as its ability to reduce tumors. Their results have been published in the Journal of Clinical Oncology.
“A genetically modified cancer-killing virus can deliver a one-two punch against tumors, destroying cancer cells from within and, at the same time, calling the immune system against them”
This genetically modified virus is injected directly into tumors, and has been designed to work against tumors in two ways. It multiplies inside cancer cells to burst them from within and also blocks a protein called CTLA-4, inducing the immune response and 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 it additional abilities to activate the immune system to act against cancer.
RP2 shrank or eliminated tumors in 10 patients
RP2 treatment succeeded in shrinking the tumors in three of the nine patients. The tumor of a patient with salivary gland cancer disappeared completely and 15 months after starting treatment she remains cancer free. The other two patients in this group had cancer of the esophagus and uveal melanoma, a rare type of eye cancer, that had spread to the liver. Their cancers shrank and were still responding 18 and 15 months after starting treatment, respectively, meaning their cancer had not progressed.
In the case of the 30 patients who received RP2 and immunotherapy with nivolumab, seven of them also benefited from the treatment. In this group, four of nine patients had melanoma skin cancer, two of eight patients with uveal melanoma eye cancer, and one in three patients with head and neck cancer saw their cancer growth stop or slow. Of the seven patients who were treated with the combination and benefited, six remained progression-free at 14 months.
The researchers looked at the patients’ biopsies before and after RP2 injections and found positive changes in the tumor’s ‘immune microenvironment’. The injections generated more immune cells in this area, including CD8+ T cells, and “turned on” genes linked to the “anti-cancer” immune response.
Most of the observed RP2 side effects were mild—the most common being fever, chills, and fatigue—and none were severe enough to require medical attention. Professor Kevin Harrington, Professor of Biological Cancer Therapies at the Institute of Cancer Research London and Consultant Oncologist at The Royal Marsden NHS Foundation Trust, who led the study, said: “Our study shows that a genetically modified virus that kills cancer can deliver a double whammy against tumors, directly destroying cancer cells from within and, at the same time, calling the immune system against them.”
A treatment option for some advanced cancers
“It is rare to see such good response rates in early-stage clinical trials, as their primary goal is to test treatment safety and they involve patients with very advanced cancers for whom current treatments have stopped working. “The results of our initial trial suggest that a genetically modified form of the herpes virus could potentially become a new treatment option for some patients with advanced cancers, including those who have not responded to other forms of immunotherapy. I am looking forward to seeing if we continue to see benefits as we treat more patients,” added Harrington.
Professor Kristian Helin, CEO of the London Institute of Cancer Research, said: “Viruses are one of humanity’s oldest enemies, as we have all seen during the pandemic. But our new research suggests we can exploit some of the features that make them defy adversaries to infect and kill cancer cells. It’s a small study, but the initial findings are promising. I am very hopeful that as this research expands, we will see patients continue to benefit.”
In fact, participating in this trial has saved the life of a 39-year-old patient named Krzysztof Wojkowski, who was diagnosed with mucoepidermoid carcinoma, a type of cancer of the salivary glands, in May 2017. This man, a London-based builder , underwent numerous surgeries and ran out of further treatment options before joining the trial in 2020.
She has now stated: “I was told that I had no options left and that I was receiving end of life care, it was devastating, so it was amazing to have the opportunity to join the trial at The Royal Marsden, it was my last lifeline. I had injections every two weeks for five weeks that completely eradicated my cancer. I have been cancer free for two years, it is a true miracle, there is no other word to describe it. I’ve been able to go back to work as a builder and spend time with my family, there’s nothing I can’t do.”
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