Marcin Kortylewski, Ph.D.
Marcin Kortylewski, Ph.D., leads an impressive slate of 2017 City of Hope grant awardees.
In January, Kortylewski, an associate professor in the Department of Immuno-Oncology, was awarded a five-year grant from the National Institutes of Health to better understand how a new type of STAT3 inhibitor works in cases of acute myeloid leukemia. The research team will recreate the human immune system within mice to see how the drug interacts with human cancer cells and the human immune system.
“The NCI/NIH funding will allow us to explain how our new CpG-STAT3 inhibitor triggers regression of leukemia,” said Kortylewski. “For the last 15 years, researchers have been devoted to finding a pharmacological drug to block STAT3 in cancer cells, which turned out to be very difficult. Instead, we have focused on using a new type of oligonucleotide drug to inhibit STAT3 in immune cells, which can disarm tumor defense systems, and then activate an attack by the immune system.”
The drug that Kortylewski and his colleagues have developed is an immune cell-selective STAT3 decoy oligodeoxynucleotide molecule. “It tricks the immune cells into picking up the drug, which then blocks STAT3 activity and stimulates an immune response to the cancer at the same time,” he explained.
Kortylewski is also working closely with Sumanta Pal, M.D., assistant professor, Department of Medical Oncology & Therapeutics Research, and an expert on genitourinary cancers. Together, they are studying the anti-tumor effects and most effective targets of the drug in cases of late-stage prostate cancer. In mice models with the disease, those that received the new version of the STAT3 inhibitor experienced a regression in prostate cancer that had metastasized to the bones. They also want to examine if the drug will allow radiation to have long-term effects in treating prostate cancer, preventing a recurrence of the disease.
Down the road, he wants to see if there might be other master regulators of tumor progression like STAT3, which could be targeted to fight cancer with few side effects.
“I chose the biomedical field because I wanted to do something meaningful, to feel like I’m contributing to society,” said Kortylewski, who was born in Poland, then trained in Germany and moved to the United States in 2002. “And I was always interested in understanding and fighting cancer. Several of my relatives fought but lost their lives to this disease, including my dad, who died of gastric cancer just three years ago.”
Kortylewski came to City of Hope after the arrival of Hua Yu, Ph.D., his mentor at the H. Lee Moffitt Cancer Center in Tampa, Florida. She is now associate chair of the Department of Immuno-Oncology at City of Hope and the Billy and Audrey L. Wilder Professor in Tumor Immunotherapy.
“I appreciate that in addition to the opportunity and ease of collaborating with many talented investigators from various disciplines, there is a strong focus here on shortening the path from bench research to clinical care,” he said. “We are thrilled to be able to develop the CpG-STAT3 inhibitor for clinical application her at City of Hope.”
For a list of all of the City of Hope researchers who have been awarded grants over the past few months, click here.