Yale researcher Dr. Kurt Schalper, assistant professor of pathology and medicine (medical oncology), who has made major breakthroughs in cancer immunotherapy, received an R37 Merit Award from the National Institutes of Health (NIH). The award — granted to just 5% of NIH-funded investigators —ensures that Schalper’s research will be funded for the next seven years.
The award supports Schalper’s groundbreaking work identifying novel pathways for cancer immunotherapy which can be used to optimally select and treat patients with non-small cell lung cancer.
Immunotherapy, which harnesses the power of the body’s immune system to target tumors, has been the next frontier for cancer treatment. In the case of non-small cell lung cancer, a class of drugs known as PD-1 axis inhibitors — immune checkpoint inhibitors — has been effective at preventing progression of the disease and prolonging life. But, Schalper said, “there is still a lot to do since most patients don’t benefit from these treatments.” However, patients receive them nonetheless, withstanding the side effects and the financial costs without clear benefit. Approximately 20% of patients with non-small cell lung cancer benefit from current PD-1 axis blockers and survive.
The R37 NIH Merit Award recognizes Schalper’s research on an alternate target for immunotherapy drugs — the LAG-3/FGL1 pathway. The protein FGL1 is a LAG-3 ligand (a molecule that binds to another molecule) produced by human cancer cells and is elevated in the blood of cancer patients. Blocking this pathway with new therapies could provide another treatment option for patients who don’t respond to existing drugs, Schalper said.
“We have established that the LAG-3/FGL1 pathway plays a prominent role in lung cancer,” said Schalper. “Now we are trying to expand our data and rapidly translate the findings into the clinic so that they can be used in patients.”
Schalper, who directs the Translational Immuno-oncology Laboratory at Yale School of Medicine and oversees 12 trainees researching cancer immunology of solid tumors, is at the forefront of several discoveries in immunotherapy research. He discovered an immunotherapy biomarker across multiple tumor types — interleukin-8 (IL-8) — the presence of which can help identify which patients will benefit from immune checkpoint inhibitors. Schalper and others looked at data from three clinical trials and found that higher levels of IL-8 corresponded to lower survival rates across tumor types. The findings appeared in the May 11, 2020 issue of Nature Medicine. A related commentary in the journal noted that the findings are “a substantial step toward the development of a readily measurable blood-based biomarker of adverse prognosis in patients treated with ICIs [immune checkpoint inhibitors].”
“These findings have had resonance in the field,” said Schalper, who adds that he expects that his discoveries related to interleukin-8 and to the new LAG-3/FGLI-1 pathway will likely converge and become complementary. One, a biomarker to help identify patients who will not respond well to traditional immune checkpoint inhibitors; the other, a biomarker to target for a new type of immunotherapy.
The R37 NIH Award goes into effect on July 1.