A genetically modified herpes simplex virus has shown promising results against advanced cancers in an early-stage clinical trial, with one patient achieving complete tumor elimination and remaining cancer-free for over a year. The findings, presented at the 2022 European Society for Medical Oncology Congress, suggest that cancer-killing viruses could offer new hope for patients who have failed to respond to conventional treatments.
Dual-Action Viral Therapy
The experimental treatment, called RP2, is a modified version of the herpes simplex virus that delivers what researchers describe as a "one-two punch" against tumors. The virus is injected directly into tumors and works through two mechanisms: it multiplies inside cancer cells to burst them from within, and it blocks a protein known as CTLA-4, which releases the brakes on the immune system and increases its ability to kill cancer cells.
RP2 has been further engineered 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.
Trial Results Show Promise
The phase I trial, conducted by researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, evaluated RP2 in 39 patients with advanced cancers including skin, oesophageal, and head and neck cancers. All participants had exhausted other treatment options, including checkpoint inhibitor immunotherapy.
Among nine patients treated with RP2 alone, three saw their tumors shrink. The most remarkable case involved Krzysztof Wojkowski, a 39-year-old builder from West London diagnosed with mucoepidermoid carcinoma, a type of salivary gland cancer. After being told there were no treatment options left and receiving end-of-life care, Wojkowski joined the trial in 2020.
"I had injections every two weeks for five weeks which completely eradicated my cancer. I've been cancer-free for two years now," Wojkowski said. "It's a true miracle, there is no other word to describe it."
The other two patients in the monotherapy 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.
Combination Therapy Results
Seven out of 30 patients who received both RP2 and the immunotherapy nivolumab also benefitted from treatment. In this combination group, four out of nine patients with melanoma skin cancer, two out of eight patients with uveal melanoma, and one out of three patients with head and neck cancer saw their cancer's growth halt or shrink. Of the seven patients receiving the combination who saw a benefit, six remained progression-free at 14 months.
Immune System Activation
Analysis of patient biopsies before and after RP2 injections revealed positive changes in the tumor's immune microenvironment. The injections led to more immune cells in the area, including CD8+ T-cells, and activated genes linked to the anti-cancer immune response.
Study leader Professor Kevin Harrington, Professor of Biological Cancer Therapies at The Institute of Cancer Research, noted the significance of these findings: "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."
Safety Profile
The treatment demonstrated a favorable safety profile, with most side effects being mild. The most common adverse events included fever, chills, and fatigue. None of the side effects were serious enough to require medical intervention.
Building on Previous Viral Therapies
This is not the first time scientists have used viruses to fight cancer. The NHS previously approved a cold-virus-based therapy called T-Vec for advanced skin cancer. Professor Harrington describes RP2 as a "souped-up version" of T-Vec, with additional modifications that enhance its cancer-killing capabilities.
Professor Kristian Helin, Chief Executive of The Institute of Cancer Research, emphasized the potential of harnessing viral properties for cancer treatment: "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."
Future Directions
The encouraging initial findings have prompted researchers to plan larger studies to further evaluate RP2's potential. The ongoing phase I trial, sponsored by manufacturer Replimune, continues to test the safety and dosage of RP2 while evaluating its tumor-shrinking capabilities.
Dr. Marianne Baker from Cancer Research UK noted that while scientists discovered viruses could help treat cancer 100 years ago, it has been challenging to harness them safely and effectively. These new findings suggest that challenge may finally be overcome, potentially changing the course of cancer treatment for patients with advanced disease.
