Novel treatment disrupts tumor immunosuppression in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, with a five-year survival rate below 10%.

University of Cincinnati Cancer Center researchers examined the unique tumor microenvironment of PDAC cells, identified a key protein that aids tumor treatment resistance, and developed a new drug targeting this protein that reduced tumor size and increased survival in animal models.

Following the publication of two manuscripts in the journal Cancers in January and April 2025, the Cancer Center's Ahmet Kaynak will present his research at the American Association for Cancer Research's Special Conference in Pancreatic Cancer Sept. 28 in Boston.

The tumor microenvironment is the ecosystem that includes the tumor and surrounding immune cells, blood vessels and other tissue. Kaynak said PDAC's microenvironment has unique characteristics that suppress the immune system's ability to attack the cancer cells (causing immunosuppression), hinder drug delivery, and promote resistance to chemotherapy, radiotherapy and immunotherapy.

There is an unmet need for the development of novel treatment approaches. In this project, we asked the question of what the factors are that lead to immunosuppression in the tumor microenvironment." 

Ahmet Kaynak, PhD, a trainee associate member of the Cancer Center and postdoctoral fellow, Hematology & Oncology Division, Department of Internal Medicine, UC's College of Medicine

Kaynak and colleagues identified that a protein called Hsp70 contributes to tumor immunosuppression. Hsp70's crucial role in cellular homeostasis was already well known, but its role and mechanism of action supporting immunosuppression in the tumor microenvironment was not widely acknowledged before this research.

The team then developed a drug called SapC-DOPG that specifically targets cancer cells by binding to phosphatidylserine, a lipid on the cells' surface. This work builds upon that of Kaynak's mentor, Xiaoyang Qi, PhD, who developed a similar drug called SapC-DOPS that is currently in Phase 2 clinical trials as a lung cancer treatment.

SapC-DOPG was designed to target Hsp70 within PDAC cells. In animal models of PDAC, the drug was well tolerated and resulted in smaller tumor size and increased survival.

"We hope to transition to clinical settings and investigate whether SapC-DOPG can be used as a therapeutic agent in pancreatic cancer patients," Kaynak said. "The safety of the analog SapC-DOPS has been proven in clinical trials with patients. We hope our novel drug can also be safely used in patients in the future."

One of Kaynak's publications on the research was selected as the Cancer Center's Trainee Associate Membership Paper of the Year in the spring, and he credits the support he has received as an early-career researcher.

"I would like to express my sincere gratitude to my mentor Dr. Qi and the UC Hematology and Oncology Division for their invaluable guidance and support throughout this project and my academic growth," he said.