UCLA researchers have developed a new immunotherapy designed to target pancreatic cancer, a disease with a five-year survival rate of only 2–3% for metastatic cases. The treatment, known as CAR-NKT cell therapy, uses engineered immune cells that can be mass-produced from donated blood stem cells and stored for immediate use.
Dr. Lili Yang, senior author of the study published in PNAS and professor at UCLA, said: “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.”
Unlike current personalized cell therapies that are costly and require weeks to manufacture, the new approach offers doses at approximately $5,000 each. The therapy leverages invariant natural killer T cells (NKT cells) equipped with a chimeric antigen receptor targeting mesothelin—a protein found on pancreatic cancer 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. “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 team used advanced preclinical models mimicking human pancreatic cancer’s challenging environment to test their approach. Dr. Caius Radu, study collaborator and UCLA professor of molecular and medical pharmacology, explained: “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… 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… They actively seek out and infiltrate the cancer wherever it’s hiding.”
Tests across different mouse models showed consistent results: slowed tumor growth and extended survival rates without significant loss of potency over time.
The platform also addresses barriers such as manufacturing complexity and cost associated with existing cell immunotherapies—treatments often delayed by weeks due to patient-specific processing requirements. Since NKT cells are naturally compatible with any immune system without causing rejection reactions, they can be produced on a large scale from donors.
Because mesothelin is also present in other cancers such as breast, ovarian, and lung cancers, this single product could potentially be applied more broadly. Preclinical studies have already shown effectiveness against triple-negative breast cancer and ovarian cancer.
“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, applications will soon be submitted to begin clinical trials under Food and Drug Administration review.
“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.”
Additional contributors include Xinyuan Shen, Enbo Zhu, Zhe Li, Jie Huang, Thuc Le and Catrina Tran.
Funding for this research came from several 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.
