UCLA researchers have developed a new immunotherapy approach for pancreatic cancer, aiming to address the challenges of treating this aggressive disease. Pancreatic cancer is known for its poor prognosis, with most patients diagnosed at an advanced stage and a five-year survival rate of only 2–3% for metastatic cases.
The therapy, called CAR-NKT cell therapy, uses engineered immune cells derived from donated blood stem cells. These cells are designed to target both primary and metastatic tumors by recognizing mesothelin, a protein commonly found on pancreatic cancer cells. The treatment can be mass-produced and stored, making it available off-the-shelf at a cost of about $5,000 per dose—significantly less than current personalized therapies.
“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 of the study and professor at UCLA.
Traditional CAR-T cell therapies have shown success in certain blood cancers but face obstacles with solid tumors like pancreatic cancer due to dense tissue barriers and immune suppression within the tumor environment. To overcome these issues, the UCLA team utilized invariant natural killer T (NKT) cells equipped with chimeric antigen receptors (CARs). This enables them to attack tumors through several mechanisms simultaneously.
“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.”
Testing in advanced preclinical models showed that CAR-NKT cells could effectively home in on tumors located not only in the pancreas but also those that had spread to organs such as the liver and lungs—a common challenge for current treatments.
“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.”
The research demonstrated that these engineered cells maintain their effectiveness even under harsh conditions typical of pancreatic tumors and show minimal signs of exhaustion over time.
Unlike existing cell therapies requiring patient-specific manufacturing processes—which are costly and take weeks—the new platform allows for large-scale production from donor stem cells because NKT cells do not trigger rejection across different individuals.
Additionally, since mesothelin is present on other cancers such as breast, ovarian, and lung cancers, this single product may potentially be used for multiple cancer types.
“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 hopes of providing more accessible treatment options 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.”
Other contributors include Xinyuan Shen, Enbo Zhu, Zhe Li, Jie Huang, Thuc Le and Catrina Tran. The project 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 departments within UCLA; and other partners.
