Opportunity: Targeting ART1 to overcome immune resistance in lung cancer treatment
Dr Erik Wennerberg
ICR lead scientists/inventors:
Dr Erik Wennerberg
Opportunity at a glance
Immune checkpoint inhibitors have become the gold standard treatment for patients with advanced non-small cell lung cancer (NSCLC), but most people do not benefit from long-term clinical responses.
Scientists at The Institute of Cancer Research, London, have identified that the expression of ART1 by tumour cells mediates immune resistance in NSCLC patients – and that ART1-inhibition can improve tumour control in preclinical models.
The development team is now seeking commercial partners, to support the clinical transition of the project to achieve maximum patient benefit.
More about targeting ART1 to overcome immune resistance in lung cancer treatment
Immune checkpoint inhibitors (ICI), alone or in combination with chemotherapy, have become the standard of care in patients with non-small cell lung cancer (NSCLC) without targetable molecular alterations. However, most patients with lung cancer either do not respond to or do not experience long-term benefits from ICI. There is an urgent need to identify other robust biomarkers predictive of response to ICI and to understand the mechanisms behind lung cancer resistance to immunotherapy.
The Institute of Cancer Research (ICR) researchers, in collaboration with scientists in New York, have discovered that the expression of mono-adenosine 5’-diphosphate (ADP)-ribotransferase 1 (ART1), an enzyme on the surface of tumour cells, mediates immune resistance in NSCLC (1). They demonstrated that high levels of ART1 on cancer cells leads to a reduction in certain immune cells (CD8+ T cells) in the tumour microenvironment. Genetic and antibody-mediated ART1 inhibition slowed tumour growth in mouse NSCLC and melanoma models.
These findings suggest that ART1 expression may have prognostic and predictive value in patients with lung cancer undergoing immunotherapy. Pharmacologic targeting of ART1 could provide a way to boost immune responses in patients with NSCLC.
Key Points
- ART1 could be developed into a biomarker test to personalise treatment with ICI in patients with advanced NSCLC – ensuring each individual receives the best treatment option while minimising unnecessary side effects.
- Therapeutic targeting of ART1 offers the potential to overcome resistance to immunotherapy – improving and widening the benefits of these drugs for lung cancer patients.
- Further work is now needed to investigate the mechanisms by which ART1 disrupts anti-tumour immune responses and whether ART1 inhibition could provide a more general strategy for overcoming immune resistance in other cancers.
Key publications
Wennerberg, E. et al. Expression of the mono-ADP-ribosyltransferase ART1 by tumor cells mediates immune resistance in non-small cell lung cancer. Sci. Transl. Med. 14, eabe8195 (2022).
Contact us
Contact:
Vibha Tamboli
Business Development Manager
The Institute of Cancer Research, London