Researchers have identified an allergy pathway that, when blocked, unleashes anti-tumour immunity in mouse models of non-small cell lung cancer (NSCLC).
And in an early parallel study in humans, combining immunotherapy with dupilumab — an Interleukin-4 (IL-4) receptor-blocking antibody widely used for treating allergies and asthma — boosted patients’ immune systems.
The study, published in the journal Nature, showed one out of the six people experienced significant tumour reduction.
“Immunotherapy using checkpoint blockade has revolutionised treatment for non-small cell lung cancer, the most common form of lung cancer, but currently only about a third of patients respond to it alone, and in most patients, the benefit is temporary,” said Miriam Merad, from the Icahn School of Medicine at Mount Sinai.
The team focussed on using single cell technology and artificial intelligence to identify molecular immune programmes that can dampen tumour immune response to checkpoint blockade.
Also known as a PD1 inhibitor, checkpoint blockade is a type of cancer immunotherapy that can unleash the cancer-killing activity of T cells.
“Using single cell technologies, we discovered that the immune cells infiltrating lung cancers, as well as other cancers we studied, exhibited characteristics of a ‘type 2’ immune response, which is commonly associated with allergic conditions like eczema and asthma,” said Nelson LaMarche, a postdoctoral research fellow at the Icahn School of Medicine at Mount Sinai.
“These results led us to explore whether we could repurpose a medication typically used for allergic conditions to ‘rescue’ or enhance tumour response to checkpoint blockade,” said Thomas Marron, Director of the Early Phase Trial Unit at Mount Sinai’s Tisch Cancer Center.
“Strikingly, we found that IL-4 blockade enhanced lung cancer response to checkpoint blockade in mice and in six lung cancer patients with treatment-resistant disease. In fact, one patient whose lung cancer was growing despite checkpoint blockade had nearly all their cancer disappear after receiving just three doses of the allergy medication, and his cancer remains controlled today, over 17 months later.”
The researchers are encouraged by the initial results but emphasise the need for larger clinical trials to validate the drug’s efficacy in treating NSCLC. Beyond the clinical trial findings, the investigators have now expanded the clinical trial, adding dupilumab to checkpoint blockade for a larger group of lung cancer patients. Through the trials, they aim to search for biomarkers that can predict which cancer patients might benefit from dupilumab treatment and which may not.