UCLA researchers have developed a new immunotherapy approach for pancreatic cancer, a disease known for its poor prognosis and limited treatment options. The therapy, called CAR-NKT cell therapy, is designed to target both primary tumors and metastases in preclinical models. According to Dr. Lili Yang, senior author of the study and professor at UCLA, “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 engineered immune cells used in this therapy are produced from donated blood stem cells and can be stored until needed. Each dose costs about $5,000, significantly less than current personalized cell therapies which often cost hundreds of thousands of dollars and require weeks to manufacture.
Pancreatic tumors are particularly difficult to treat due to their dense protective barriers and ability to evade immune detection. To address these challenges, the UCLA team utilized invariant natural killer T cells (NKT cells) modified with a chimeric antigen receptor (CAR) targeting mesothelin—a protein found on pancreatic cancer cells. Dr. Yanruide (Charlie) Li, first author of the study, explained: “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.”
Testing in advanced preclinical models demonstrated that CAR-NKT cells could locate and infiltrate tumors not only in the pancreas but also those that had spread to organs such as the liver and lungs. 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… They actively seek out and infiltrate the cancer wherever it’s hiding.” Across various mouse models representing different stages and locations of pancreatic cancer, CAR-NKT cell therapy slowed tumor growth and extended survival without showing signs of exhaustion commonly seen with other cell therapies.
A key advantage of this platform is its potential accessibility for more patients due to simplified manufacturing processes and reduced costs compared to traditional patient-specific approaches. Since NKT cells are compatible across different individuals without causing rejection reactions, they can be mass-produced from donor stem cells for broad use.
The technology may also apply beyond pancreatic cancer; because mesothelin is present in other cancers such as breast, ovarian, and lung cancers, there is potential for broader applications using a single product line.
Li stated: “We hear from people almost every day wanting to know if our new cell therapy can help treat their loved ones… Meeting this critical unmet medical need is what drives us.” With preclinical studies complete, preparations are underway for FDA submissions seeking approval for clinical trials.
Yang emphasized: “Pancreatic cancer patients need better treatment options now… 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 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; UCLA’s department of microbiology, immunology and molecular genetics; UCLA Office of the Chancellor; and UCLA Goodman-Luskin Microbiome Center.
