UCLA researchers have developed a new immunotherapy that may improve treatment options for pancreatic cancer, one of the most lethal forms of the disease. Pancreatic cancer is often diagnosed after it has spread, with a five-year survival rate for metastatic cases at about 2–3%. Median survival is typically measured in months.
The study, published in PNAS, describes a therapy called CAR-NKT cell therapy. This approach uses engineered immune cells to target and destroy pancreatic tumors, including those that have metastasized to other organs.
“Developing a therapy that targets both the primary tumor and its metastases in preclinical studies — one that can be ready to use off-the-shelf — represents a fundamental shift in how we might treat this disease,” said Dr. Lili Yang, senior author and professor at UCLA.
Unlike current personalized cell therapies, which are expensive and require weeks to manufacture from each patient’s own cells, the new therapy can be mass-produced from donated blood stem cells and stored for immediate use. Each dose is estimated to cost around $5,000.
CAR-T cell therapies have shown success against certain blood cancers but face challenges with solid tumors like pancreatic cancer due to dense tissue barriers and immune suppression within tumors. The UCLA team addressed these obstacles by using invariant natural killer T (NKT) cells equipped with a chimeric antigen receptor targeting mesothelin—a protein found on pancreatic cancer cells.
“We’re essentially surrounding the tumor with no escape routes,” said Dr. Yanruide (Charlie) Li, first author of the study. “Even when the cancer tries to evade one attack pathway by changing its molecular signature, our therapy is hitting it from multiple other angles at the same time. The tumor simply can’t adapt fast enough.”
The research used advanced preclinical models designed to closely mimic human pancreatic cancer conditions. These included orthotopic models where tumors grow in the pancreas itself and metastatic models targeting common sites like the liver.
“Many treatments that looked promising in simpler lab models have completely failed in patients,” said Dr. Caius Radu, study collaborator and UCLA professor. “We used orthotopic models where tumors grow in the pancreas itself, and metastatic models targeting the liver, which is one of the most common and deadly sites of spread. The fact that this therapy worked in both settings is genuinely encouraging.”
According to Li, “These cells express high levels of chemokine receptors — molecular GPS systems that guide them directly to tumor sites.” He added: “When the tumor is in the lung, they go to the lung. When it’s in the pancreas, they go to the pancreas. They actively seek out and infiltrate the cancer wherever it’s hiding.”
In various mouse models—including those with tumors growing under skin or spreading throughout organs—the CAR-NKT cells slowed tumor growth and extended survival times while maintaining their effectiveness over time.
The platform also aims to make cell therapies more accessible by reducing manufacturing complexity and cost as well as shortening wait times for patients who need rapid intervention.
Since NKT cells are naturally compatible across different immune systems without causing rejection reactions, they can be produced at scale from donor stem cells—potentially allowing one donor’s cells to supply thousands of treatments.
Because mesothelin is also present in breast, ovarian, and lung cancers, this single product could potentially be used against several types of cancer. The team has already shown effectiveness against triple-negative breast cancer and ovarian cancer in separate studies.
“We hear from people almost every day wanting to know if our new cell therapy can help treat their loved ones,” Li said. “Meeting this critical unmet medical need is what drives us.”
With preclinical studies complete, applications will soon be submitted to begin clinical trials with FDA oversight.
“Pancreatic cancer patients need better treatment options now,” Yang said. “We’ve developed a therapy that’s potent, safe, scalable and affordable. The next critical step is proving it can deliver the same results in patients that we’ve seen in our preclinical work.”
Other contributors include Xinyuan Shen, Enbo Zhu, Zhe Li, Jie Huang, Thuc Le and Catrina Tran.
The research received support from organizations such as the California Institute for Regenerative Medicine; Department of Defense; UCLA Broad Stem Cell Research Center; Wendy Ablon Trust; Parker Institute for Cancer Immunotherapy; UCLA departments; Office of Chancellor; and Goodman-Luskin Microbiome Center.
