WORCESTER — An experimental mRNA immunotherapy developed by UMass Chan Medical School scientists Marcus Ruscetti, PhD, and Chaitanya Naimesh Parikh, PhD’26, eliminated pancreatic tumors in approximately half of the mice treated during a preclinical study.
According to UMass Chan Medical School, the study, published in Nature Communications, tested a treatment that combined immune-signaling cytokine mRNAs and tumor-associated antigen mRNAs in a single injection designed to help the immune system recognize and attack pancreatic ductal adenocarcinoma. Approximately 50 percent of the mice with pancreatic cancer treated with the mRNA immunotherapeutic cocktail experienced complete tumor responses and remained disease-free for as long as one year after treatment ended, potentially indicating that their immune systems had developed a lasting memory of the cancer cells.
“It’s unheard of to get a response like this in these models of pancreatic cancer,” said Dr. Parikh. “There have been a lot of drugs tried in the lab that have had good initial responses in mice but ultimately the cancer always comes back. This is the only study I’ve seen that has achieved durable tumor protection.”
Pancreatic ductal adenocarcinoma is the most common and aggressive form of pancreatic cancer. According to UMass Chan Medical School, since its early symptoms can be difficult to detect, the disease is often diagnosed after it has spread to other organs. The five-year survival rate for pancreatic cancer is 3 percent at stage IV and 13 percent across all stages.
Pancreatic tumors can also build a fibrotic barrier that prevents immune cells from reaching and attacking the cancer. The experimental treatment was designed to weaken that barrier while helping the immune system identify the tumor cells as foreign material.
The researchers injected the mice with a combination of five cytokine mRNAs and three tumor-antigen mRNAs. They subsequently observed reduced fibrotic material and increased tumor cell necrosis.
“This is a first-of-its-kind approach combining cytokine mRNAs with tumor associated antigen mRNA that could pave the path for effective immunotherapy for pancreatic ductal adenocarcinomas,” Dr. Parikh said. “Beyond this cancer, this mRNA immunotherapy strategy has the capacity to be modular and can potentially be used as a platform to treat other types of immune-resistance cancers simply by swapping out different mRNA sequences.”
The approach remains in the preclinical stage and has not yet been tested in patients.
“Going from mice into patients takes a huge effort and is never a sure thing,” said Dr. Ruscetti, an associate professor of molecular, cell and cancer biology. “However, if there was one approach I had to bet on being successful, this is the one. And that’s what we’re doing.”
According to UMass Chan Medical School, initial funding for the study was provided by the Worcester-based Pancreatic Cancer Alliance. Researchers are now working to develop a version of the treatment suitable for a potential investigational new drug application and future clinical trials.
