An estimated 5% of all NIH-funded researchers are selected to receive this multiyear merit award.
Schalper, an assistant professor of pathology and medicine at Yale School of Medicine, has focused on identifying new signaling cascades that could be used as therapeutic targets to develop new immunotherapies for patients with non-small cell lung cancer (NSCLC).
His work was motivated by the low percentage (20%) of NSCLC patients who actually respond to treatment with standard immune checkpoint inhibitors, a class of immunotherapy agents that block the activity of certain proteins used by cancer cells to avoid being targeted and destroyed by immune cells.
“There is still a lot to do since most patients don’t benefit from these treatments,” Schalper said in a university press release.
During earlier work into alternative targets that might help those who failed to respond to standard treatments, Schalper and his colleagues found a signaling cascade — the LAG-3/FGL1 pathway — that seemed a promising candidate.
In a study published in the journal Cell, they reported that FGL1, a protein normally released by the liver in low amounts, is overproduced by cancer cells. When FGL1 interacts with its receptor LAG-3, which is found on the surface of immune cells, it shuts these cells down, allowing cancer cells to evade the body’s natural defense mechanisms.
Schalper and his team believe agents capable of blocking the interaction between FGL1 and LAG-3 may be promising candidates to treat cancer patients who do not respond to existing therapies.
“We have established that the LAG-3/FGL1 pathway plays a prominent role in lung cancer,” Schalper said. “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 was also involved in a recent groundbreaking discovery in the field of immunotherapy. In a study published in the journal Nature Medicine, he and his colleagues reported the discovery of an immunotherapy biomarker, called interleukin-8 (IL-8), in different types of tumors.
According to the team, the presence of IL-8 on tumors can help predict those patients more likely to respond to treatment with immune checkpoint inhibitors.
After reviewing data from three Phase 3 clinical trials enrolling people with advanced cancers being treated with Opdivo (nivolumab) and/or Yervoy (ipilimumab), the researchers found that patients with higher levels of IL-8 in their tumors were also those with the poorest survival rates.
“These findings have had resonance in the field,” Schalper said, adding that he is anticipating both discoveries will converge and complement each other in the future.
While IL-8 can help physicians identify those who are unlikely to respond to conventional therapies, the LAG-3/FGL1 pathway can provide a way of better treating these patients.
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