Researchers at Mount Sinai’s Icahn School of Medicine have discovered an allergy pathway that, when inhibited, activates antitumor immunity in animal models of non-small cell lung cancer (NSCLC).
In preliminary human research, combining immunotherapy with dupilumab – an Interleukin-4 (IL-4) receptor-blocking antibody widely used to treat allergies and asthma – improved patients’ immune systems, with one out of six patients having significant tumor decrease. The findings were published in Nature on December 6th.
“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.
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.
Nelson LaMarche
“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.”
Checkpoint blockade, also known as a PD1 inhibitor, is a kind of cancer immunotherapy that can activate T cells’ cancer-killing function.
“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 Nelson LaMarche, Ph.D., a postdoctoral research fellow in Dr. Merad’s lab.
“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.
“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 preliminary findings, but underline the necessity for larger clinical trials to prove the drug’s efficacy in treating NSCLC.
Beyond the clinical trial findings reported in the current Nature paper, the investigators have now expanded the clinical trial, adding dupilumab to checkpoint blockade for a larger group of lung cancer patients, and Dr. Marron recently received a grant from the Cancer Research Institute to study the effects in early-stage lung cancer as well. These trials are looking for biomarkers that can predict which cancer patients will benefit from dupilumab treatment and which will not.
“The Cancer Research Institute (CRI) proudly supports the visionary team at the Icahn School of Medicine at Mount Sinai in our never-ending pursuit of progress.” Their findings reinforce our commitment to funding research from the lab to clinical implementation, fueled by cutting-edge technology and data. We’re excited to see our assistance provide new hope by identifying paths to improve checkpoint blockade responses. “We champion this discovery and take pride in being a part of its journey from lab to the clinic, reinforcing our commitment to transforming lives,” said CRI CEO and head of scientific affairs Jill O’Donnell-Tormey, Ph.D.
