UCLA Scientists Develop One-Product-Fits-All Immunotherapy for Breast Cancer
Triple-negative breast cancer is among the most aggressive cancers because it lacks the three main targets that make other types of breast cancers more treatable.
UCLA researchers recently developed a therapy that could fundamentally change the treatment plan for this deadly disease. In a study published in the Journal of Hematology & Oncology, the team details how this new type of immunotherapy, called CAR-NKT cell therapy, could attack tumors from multiple fronts.
“Patients with triple-negative breast cancer have been waiting far too long for better treatment options,” said senior author Lili Yang, PhD, a professor of microbiology, immunology and molecular genetics and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. “To finally have a therapy that shows superior cancer-fighting ability — and to be just one step away from clinical testing — is incredibly exciting.”
The therapy uses engineered immune cells called CAR-NKT cells, which can be mass-produced from donated blood stem cells and stored ready-to-use. This approach offers an immediate treatment option at a significantly lower cost than current personalized cell therapies, which can cost hundreds of thousands of dollars.
A triple threat against a triple-negative cancer
CAR-T cell therapies turn patients’ own immune cells into precision weapons, transforming treatment for certain blood cancers. However, these therapies have struggled against solid tumors such as breast cancer, which employ sophisticated defense mechanisms and constantly evolve to evade treatment.
To defeat them, the UCLA team’s cell therapy harnesses a rare type of immune cell called invariant natural killer T cell, or NKT cell. When equipped with a chimeric antigen receptor, or CAR, targeting mesothelin — a protein found on triple-negative breast cancer cells — these potent tumor-fighting cells gain the ability to recognize and destroy cancer through three distinct mechanisms.
The first mechanism uses the engineered CAR to target mesothelin, which is associated with more aggressive, metastatic disease. The second leverages the cells’ natural killer receptors that recognize more than 20 molecular markers, making it nearly impossible for tumors to evade them all. The third employs the cells’ unique T-cell receptor to reshape the tumor microenvironment by eliminating immunosuppressive cells.
“We’re not just targeting one molecular marker on cancer cells — we’re identifying dozens of them simultaneously,” said first author Yanruide (Charlie) Li, PhD, a postdoctoral scholar in the UCLA Broad Stem Cell Research Center Training Program. “It’s like attacking a fortress from every direction at once. The cancer simply can’t adapt fast enough to escape.”
The CAR-NKT cells successfully killed cancer cells in every tumor sample from patients with late-stage metastatic breast cancer, also eliminating the immunosuppressive cells that tumors recruit as protectors.
Engineering universal accessibility
Beyond its cancer-fighting capabilities, the CAR-NKT platform addresses barriers that limit cell therapy access: manufacturing complexity and cost.
Current cellular immunotherapies require collecting each patient’s immune cells, shipping them to laboratories for genetic modification, then returning the customized product into the patient weeks later — a very costly process that can create dangerous delays in treating aggressive cancers.
Dr. Yang’s team’s approach is fundamentally different. Because NKT cells naturally work with any immune system, they can be mass-produced from donated blood stem cells. One donation could generate enough cells for thousands of treatments, reducing costs to approximately $5,000 per dose.
One product to tackle multiple cancers
The therapy’s promise extends beyond triple-negative breast cancer. Since mesothelin is also highly expressed in ovarian, pancreatic and lung cancers, the same cell product could treat multiple other difficult-to-address cancer types.
“This is really a platform technology,” said Dr. Yang, who’s also a member of the UCLA Health Jonsson Comprehensive Cancer Center.
With all preclinical studies complete for triple-negative breast cancer and ovarian cancer, the team prepares to submit applications to the Food and Drug Administration to begin clinical trials.
“We’ve walked 99 steps to get here,” Dr. Yang said. “We’re missing just one final step to begin clinical testing and demonstrate what this promising therapy can really do for patients.”
Additional authors are: Xinyuan Shen, Yichen Zhu, Zhe Li, Ryan Hon, Yanxin Tian, Jie Huang, Annabel Zhao, Nathan Ma, Catherine Zhang, David Lin, Karine Sargsyan and Yuan Yuan.
The research was supported by the California Institute for Regenerative Medicine, the Department of Defense, the UCLA Broad Stem Cell Research Center, the Wendy Ablon Trust, the Parker Institute for Cancer Immunotherapy, UCLA’s department of microbiology, immunology and molecular genetics, the UCLA Office of the Chancellor and the UCLA Goodman-Luskin Microbiome Center.
