Targeting ART1 to Overcome Immune Resistance in Lung Cancer

Background

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.

Technology Overview

Researchers at The Institute of Cancer Research, London, have identified that the expression of ART1 by tumour cells mediates immune resistance in non‑small cell lung cancer (NSCLC) patients – and ART1 inhibition can improve tumour control in preclinical models.

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.

Stage of Development

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.

Benefits

• 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.

Opportunity

The development team is now seeking commercial development partners to support the transition of this research into the clinic to achieve maximum patient benefit.