UCLA researchers have developed a new immunotherapy approach that may improve treatment for pancreatic cancer, one of the most lethal forms of cancer. The five-year survival rate for metastatic pancreatic cancer remains at about 2–3%, with median survival measured in months.
The study, published in PNAS, describes a therapy called CAR-NKT cell therapy. This treatment uses engineered immune cells to target and destroy pancreatic tumors, including those that have spread 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’s Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.
Unlike current personalized cell therapies, which require weeks to manufacture and can cost hundreds of thousands of dollars, the new method allows for mass production from donated blood stem cells. Each dose could be available immediately at an estimated $5,000 per treatment.
Pancreatic tumors often evade existing treatments by creating dense tissue barriers and altering their molecular markers. To address these challenges, Yang’s team used invariant natural killer T (NKT) cells equipped with a chimeric antigen receptor (CAR) targeting mesothelin—a protein present on pancreatic cancer cells. This modification enables the immune cells to attack tumors through multiple mechanisms.
“We’re essentially surrounding the tumor with no escape routes,” said Dr. Yanruide (Charlie) Li, first author and postdoctoral scholar at UCLA Broad Stem Cell Research Center Training Program. “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.”
Conventional CAR-T cell therapies often struggle to reach metastatic sites like the lungs or liver due to tissue barriers. The UCLA team tested their therapy using advanced models designed to replicate human pancreatic cancer conditions.
“Many treatments that looked promising in simpler lab models have completely failed in patients,” said Dr. Caius Radu, study collaborator and professor at UCLA. “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.”
In tests across various mouse models—including those with tumors growing within the pancreas or spreading elsewhere—the CAR-NKT cells consistently slowed tumor growth and extended survival times.
“These cells express high levels of chemokine receptors — molecular GPS systems that guide them directly to tumor sites,” Li explained. When placed into mice with different tumor locations, these therapeutic cells actively sought out and infiltrated cancers wherever they were found.
A key advantage is accessibility: NKT cells are compatible with any immune system without causing rejection reactions. They can be produced on a large scale from donor stem cells—one donor could provide enough material for thousands of doses—reducing costs and wait times compared to traditional patient-specific approaches.
The therapy targets mesothelin, also found in breast, ovarian, and lung cancers; previous studies showed effectiveness against triple-negative breast cancer and ovarian cancer as well.
“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 testing complete, researchers are preparing applications for clinical trials with the Food and Drug Administration.
“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.
Funding came 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; several UCLA departments; Office of the Chancellor; and Goodman-Luskin Microbiome Center.
