Antibody-immunotherapy combination shows promise in lung cancer

In an early human study, US researchers have found that combining immunotherapy with dupilumab, an Interleukin-4 (IL-4) receptor-blocking antibody, boosted the immune system of lung cancer patients. Dupilumab is used widely as an allergy and asthma treatment, stated the authors of the corresponding research paper, which has been published in Nature.

“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,” noted first study author Nelson LaMarche.

Maximising the benefits of cancer immunotherapy

“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,” Dr Thomas Marron, PhD, Director of the Early Phase Trial Unit at Mount Sinai’s Tisch Cancer Center, and co-senior author of the study continued.

In the study, IL-4 blockade enhanced lung cancer response to checkpoint blockade in six lung cancer patients with treatment-resistant disease, Dr Marron added.

The investigators highlighted in the paper that “one out of six patients, drove a near-complete clinical response two months after treatment.”

A 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,” Dr Marron shared.

“Immunotherapy using checkpoint blockade has revolutionised treatment for non-small cell lung cancer (NSCLC)… but currently only about a third of patients respond to it alone, and in most patients, the benefit is temporary,” commented senior study author Dr Miriam Merad, Director of the Marc and Jennifer Lipschultz Precision Immunology Institute and Chair of the Department of Immunology and Immunotherapy at the Icahn School of Medicine at Mount Sinai.

In the paper, LaMarche et al. concluded that the study “defines a central role for IL-4 in controlling immunosuppressive myelopoiesis in cancer [and] identifies a novel combination therapy for immune checkpoint blockade in humans.”

Future clinical studies

The researchers acknowledged that larger clinical trials are needed to validate the drug’s efficacy in treating NSCLC as shown in this initial human trial. Therefore, the investigators have expanded the clinical trial, adding dupilumab to checkpoint blockade for a larger group of lung cancer patients.

The trial was funded by grants from the National Institutes of Health (NIH), Bristol Myers Squibb Irvington Research Fellowship the AstraZeneca Immuno-oncology Research Fellowship