Immunovirotherapies - a powerful combination?
This month’s Nature Reviews Cancer discusses two recent papers that indicate potential benefits of combining viral- and immuno- therapeutic approaches (Research Highlights: Viral Reprogramming).
Within the rapidly advancing field of cancer immunotherapies, a big focus is currently on developing immune checkpoint inhibitors. These work by targeting proteins that keep immune responses in check, enabling T cells to kill cancer cells more effectively.
Examples of such targets include the programmed cell death protein 1(PD-1) and programmed cell death 1 ligand 1 (PD-L1), with a huge volume of current studies involving anti-PD-1/L1 combinations, which I highlighted in my recent post about the immuno-oncology landscape.
New approaches for solid tumours
But results from clinical studies so far show that only a minority of patients with solid tumours benefit from immune checkpoint inhibitors, with the response correlating with pre-existing tumour-infiltrating cytotoxic T-cells and PD-L1 levels. So it has been hypothesised that using a combination of immunotherapeutic approaches might improve their effectiveness.
Two new studies, both published in Science Translational Medicine, test this theory by using oncolytic viruses combined with immune checkpoint inhibitors in breast and brain tumours – both cancer types that have so far proven refractory to treatment with these immunotherapies.
Bourgeois-Daigneault et al. injected Maraba rhabdovirus into tumours into a mice pre-clinical model that follows the course of treatment for patients with triple negative breast cancer (TNBC).
Samson et al. carried out a phase 1b clinical trial involving nine patients with recurrent high-grade gliomas or brain metastases who were given human Orthoreovirus intravenously before neurosurgery.
Both studies made an important observation – virus infection triggers the upregulation of immune-response genes. In support of this, they detected more tumour-infiltrating T-cells and other immune cells in both human brain tumours and mouse TNBCs after viral treatment. And they also saw elevated PD-L1 compared to control tumours, leading them to the hypothesis that increased T cell checkpoint inhibition might be dampening the tumour response.
Piecing everything together, both teams recognised that combining immune checkpoint inhibition and viral therapy together might prove fruitful.
Samson et al. then went onto demonstrate that initial treatment with intravenous reovirus in a mouse model of glioma followed by anti-PD-1, improves survival compared to using either therapy alone.
Similarly, Bourgeois-Daigneault et al. showed that using Maraba infusion before surgical removal of the primary tumour and immune checkpoint blockade led to a complete response in 60-90% of mice after they were ‘rechallenged’ by orthotopically implanting secondary tumours after surgery.
Both studies suggest that immunovirotherapy combinations could prove a powerful approach in boosting the cancer-immune response. We look forward to seeing the results from more studies that are likely to be sparked by these encouraging results.
Keeping the cancer-immune setpoint up-to-date
In this rapidly evolving field of research, it's hard to keep up-to-date with everything that's being published - we need a collective approach.
Are these interesting new studies already referenced in the cancer-immune setpoint interactive figure? Where do you think they best fit? Please go to the framework and add your comments (n.b. you’ll need to be on a computer, rather than mobile!) – we need your help to keep on updating it as the avalanche of new data in these field continues to be published.
To help get you started, please follow our a simple step-by-step guide in our ‘how to’ post.
Dart, A. Viral Reprogramming. Nature Reviews Cancer, published online 9 Feb 2018. doi:10.1038/nrc.2018.12
Bourgeois-Daigneault, MC et al. Neoadjuvant oncolytic virotherapy before surgery sensitizes triple-negative breast cancer to immune checkpoint therapy. Sci Transl Med. 10 eaao1641 (2018)
Samso, A et al. Intravenous delivery of oncolytic reovirus to brain tumour patients immunologically primers for subsequent checkpoint blockade. Sci Transl Med. 10, eaam7577 (2018)