In mice models of Non-Small Cell Lung Cancer (NSCLC), a group of researchers at the Icahn School of Medicine at Mount Sinai have discovered an allergy pathway that, when inhibited, releases antitumor immunity.
Combining immunotherapy with dupilumab, an Interleukin-4 (IL-4) receptor-blocking antibody often used to treat allergies and asthma, enhanced patients’ immune systems in an early parallel research conducted in humans. Of the six patients, one had a substantial reduction in tumor size.
The findings were published in the December 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.
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.
Senior study author Miriam Merad, MD, PhD
Checkpoint blockade, another name for a PD1 inhibitor, is a kind of cancer immunotherapy that can activate T cells’ capacity for attacking tumors.
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.
First study author Nelson LaMarche, PhD
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.
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
Thomas Marron, MD, PhD, Director of the Early Phase Trial Unit at Mount Sinai’s Tisch Cancer Center
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Although the first results are positive, the researchers stress that bigger clinical studies must be conducted to verify the effectiveness of the medication in treating NSCLC. The researchers are currently extending the clinical trial, adding dupilumab to checkpoint blockade for a larger group of lung cancer patients, beyond the clinical trial results published in the current Nature paper. In addition, Dr. Marron recently received a grant from the Cancer Research Institute to investigate the effects of early-stage lung cancer as well. They are looking for biomarkers through this research that might predict which cancer patients may benefit and which may not from dupilumab treatment.
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In our relentless pursuit of progress, the Cancer Research Institute (CRI) proudly supports the visionary team at the Icahn School of Medicine at Mount Sinai. Their findings validate our commitment to funding research across the entire discovery continuum, from the lab to clinical implementation, driven by cutting-edge technology and data.
We’re eager to witness our support delivering new hope by uncovering pathways to enhance checkpoint blockade responses. We champion this discovery and take pride in being part of its journey from lab to clinic, reinforcing our commitment to transforming lives.
Jill O’Donnell-Tormey, PhD, CEO and director of scientific affairs at CRI
Source: Mount Sinai Press Release
Journal Reference: LaMarche, N. M., Hegde, S., Park, M. D., Maier, B. B., Troncoso, L., Le Berichel, J., Hamon, P., Belabed, M., Mattiuz, R., Hennequin, C., Chin, T., Reid, A. M., Nemeth, E., Zhang, R., Olson, O. C., Doroshow, D. B., Rohs, N. C., Gomez, J. E., Veluswamy, R., . . . Merad, M. (2023). An IL-4 signalling axis in bone marrow drives pro-tumorigenic myelopoiesis. Nature, 1-9. https://doi.org/10.1038/s41586-023-06797-9
Report: Achuth B S
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