In early trials, one quarter of terminally-ill cancer patients who had exhausted all other treatments saw their tumours completely eradicated or shrunk after being treated with a genetically-engineered version of the herpes virus.
The therapy, developed by scientists from the Institute for Cancer Research in London, infects and destroys cancer cells while also rallying the immune system, reports The Telegraph.
The genetically engineered virus, called RP2, is injected directly into the tumour where it multiplies, causing cancer cells to burst from within. It also blocks a protein called CTLA-4, which dials down the immune system, giving the body more ammunition to fight off the cancer. In addition, the virus also produces molecules, which spark the immune system into action against cancer.
The therapy was tested on 39 patients with cancers that included skin, oesophageal and head and neck cancer.
Results showed that around one quarter saw a benefit.
The herpes simplex virus is a common infection, which many people already carry latently without problems.
The researchers looked at patient biopsies before and after RP2 injections and found positive changes in the tumour’s “immune microenvironment” – the area immediately around the tumour. Injections led to more immune cells in the area, including CD8+ T-cells, and “switched on” genes linked to the “anti-cancer” immune response.
Most side effects of RP2 were mild – some of the most common were fever, chills, and fatigue. None of the side effects was serious enough to require medical intervention.
Professor Kristian Helin, chief executive of The Institute of Cancer Research, London, said: “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.
“It’s a small study but the initial findings are promising.”
Potential to become new treatment option
Study leader Kevin Harrington, professor of biological cancer therapies at The Institute of Cancer Research, said: “Our study shows that a genetically engineered, cancer-killing virus can deliver a one-two punch against tumours – directly destroying cancer cells from within while also calling in the immune system against them.
“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.”
The research was presented at the 2022 European Society for Medical Oncology Congress (ESMO), and the team is hoping to move to bigger trials.
Study details
An open-label, multicenter, phase I study of RP2 as a single agent and in combination with nivolumab in patients with solid tumors: Safety, efficacy, and biomarker results
K.J. Harrington, J.J. Sacco, A. Olsson-Brown, T. Chan, P. Nenclares, I. Leslie, P. Bommareddy, C. Ahlers, J. Wolff, M.R. Middleton.
Presented at the ESMO congress on 10 September 2022
Background
RP2 is an enhanced potency oncolytic herpes simplex virus (HSV) -1 expressing GM-CSF, a fusogenic protein (GALV-GP R-), and an anti-CTLA-4 antibody-like molecule that is being evaluated in an open-label, multicentre, phase 1 clinical trial as monotherapy and combined with nivolumab (nivo). Here, we present updated safety, efficacy, and biomarker data of RP2 ± nivo.
Methods
After determination of the RP2D (106 PFU/mL intratumorally (IT) once followed by up to 7 additional doses of 107 PFU/mL via IT), a cohort of 30 patients (pts) was enrolled and treated with RP2 combined with nivo (240 mg Q2W for 4 months from the second RP2 dose, then 480 mg Q4W for 20 months). Responses were assessed using modified RECIST v1.1.
Results
Objective responses with RP2 monotherapy were observed in 3 out of 9 pts including 1 CR for ≥15 months in mucoepidermoid carcinoma, 1 PR for ≥18 months in esophageal cancer with liver metastases, 1 PR in uveal melanoma with liver metastases that progressed at 15 months. Objective responses with RP2 + nivo treatment were 44.4% in cutaneous melanoma (4/9), 25% in uveal melanoma (2/8), and 33% in SCCHN (1/3) pts. All seven responding patients had previously failed anti-PD-1 therapy, with all but one response durable to date for >425 days. The most common adverse events (grade 1-2) were pyrexia, chills, influenza-like illness, fatigue, and pruritus. No grade 4-5 events were observed. Immunohistochemistry (IHC) analysis indicated robust increases in CD8 T cell influx, PD-L1 expression, and an increase in the CD8/foxp3+ cell ratio. Clinical responses were independent of baseline CD8 T cell infiltration, PD-L1 expression levels, and prior anti-PD-1 therapy status.
Conclusions
RP2 ± nivo demonstrated good tolerability and durable systemic responses in pts with difficult-to-treat, heavily pretreated and anti-PD-1 failed advanced cancers. These data continue to support the hypothesis that oncolytic delivery of anti-CTLA-4 into tumours, with accompanying antigen release, presentation and immune activation, can provide potent systemic anti-tumour effects.
ESMO presentation (Open access)
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