UCLA researchers have developed a new immunotherapy that may provide an effective treatment for pancreatic cancer, one of the most lethal forms of the disease. The therapy, known as CAR-NKT cell therapy, is designed to target and destroy pancreatic tumors, including those that have spread to other organs.
Pancreatic cancer has a five-year survival rate of only 2–3% for metastatic cases, with most patients diagnosed after the disease has already advanced. Current treatments offer limited success and are often costly and time-consuming.
Dr. Lili Yang, senior author of the study and professor at UCLA, explained the significance of their approach: “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.”
The new therapy uses engineered immune cells called invariant natural killer T cells (NKT cells), which are modified with a chimeric antigen receptor (CAR) targeting mesothelin—a protein found on pancreatic cancer cells. These CAR-NKT cells can be mass-produced from donated blood stem cells and stored for immediate use. This process allows for rapid treatment delivery at an estimated cost of $5,000 per dose, much lower than current personalized cell therapies.
First author Dr. Yanruide (Charlie) Li highlighted the multi-faceted attack strategy: “We’re essentially surrounding the tumor with no escape routes. 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.”
Traditional CAR-T cell therapies have had success against some blood cancers but face challenges with solid tumors like pancreatic cancer due to dense tissue barriers and immune suppression within tumors. The UCLA team’s preclinical models mimicked these harsh conditions more closely than standard lab tests.
Study collaborator Dr. Caius Radu noted: “Many treatments that looked promising in simpler lab models have completely failed in patients. 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.”
Li added: “These cells express high levels of chemokine receptors — molecular GPS systems that guide them directly to tumor sites,” explaining their ability to find and infiltrate tumors wherever they appear.
In tests across different mouse models—including primary pancreatic tumors and those spread to other organs—the CAR-NKT cell therapy consistently slowed tumor growth and extended survival times while maintaining effectiveness even under inflammatory conditions typical for these cancers.
Unlike existing immunotherapies requiring patient-specific manufacturing over several weeks, NKT cells’ compatibility with any immune system enables mass production from donor stem cells—potentially allowing one donor’s contribution to supply thousands of doses.
Because mesothelin is also present in breast, ovarian, and lung cancers, this single product could potentially be used across multiple types of cancer as demonstrated by its 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 testing completed, UCLA researchers plan to submit applications to begin clinical trials with hopes that results will translate into improved outcomes for patients.
“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.”
The research received support from organizations including the California Institute for Regenerative Medicine; Department of Defense; UCLA Broad Stem Cell Research Center; Wendy Ablon Trust; Parker Institute for Cancer Immunotherapy; various UCLA departments; Office of the Chancellor; and Goodman-Luskin Microbiome Center.
