In an early parallel study in humans with non-small cell lung cancer, combining immunotherapy with dupilumab—an Interleukin-4 (IL-4) receptor-blocking antibody widely used for treating allergies and asthma—boosted patients’ immune systems, with one out of the six experiencing significant tumor reduction.
Researchers of the study also identified an allergy pathway that, when blocked, unleashes antitumor immunity in mouse models of non-small cell lung cancer.
The findings by researchers at the Icahn School of Medicine at Mount Sinai were described in the Dec 6 issue of Nature.
“Immunotherapy using checkpoint blockade has revolutionized 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,” says senior study author Miriam Merad, MD, PhD, 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 a release. “A big focus of our program TARGET is to use single-cell technology and artificial intelligence to identify molecular immune programs that can dampen tumor 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,” says first study author Nelson LaMarche, PhD, a postdoctoral research fellow in the lab of Merad, in a release.
“These results led us to explore whether we could repurpose a medication typically used for allergic conditions to ‘rescue’ or enhance tumor response to checkpoint blockade,” says Thomas Marron, MD, PhD, director of the Early Phase Trial Unit at Mount Sinai’s Tisch Cancer Center and co-senior author of the study, in a release. “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 emphasize the need for larger clinical trials to validate the drug’s efficacy in treating non-small cell lung cancer. 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, and Marron recently received a grant from the Cancer Research Institute to study the effects in early-stage lung cancer as well.
Through these trials, they are searching for biomarkers that can predict which cancer patients might benefit from dupilumab—sold under the brand name Dupixent—treatment and which may not.
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