UCLA researchers announced on Mar. 16 the development of a new immunotherapy that could improve treatment for aggressive forms of endometrial cancer, according to a study published in Experimental Hematology & Oncology.
Endometrial cancer is the most common gynecologic cancer in the United States, with survival rates declining over recent decades. The most aggressive subtypes, such as uterine papillary serous carcinoma, account for only 10% of diagnoses but nearly 40% of deaths.
The research team described how their CAR-NKT cell therapy outperformed current immunotherapies in fighting endometrial cancer. "Across all forms of endometrial cancer, recurrence remains one of the greatest challenges - and it's especially frequent and devastating in aggressive subtypes," said Dr. Sanaz Memarzadeh, co-senior author and member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. "Patients often discover the cancer has returned after undergoing a combination of surgery, chemotherapy and radiation, so it's crucial that we devise and test new therapeutic strategies that can help save women's lives."
Unlike existing personalized immunotherapies that are costly and time-consuming to produce, this new approach uses an off-the-shelf production platform designed to make treatment more accessible. The therapy employs invariant natural killer T cells (NKT cells) equipped with a chimeric antigen receptor (CAR) targeting mesothelin—a protein found on endometrial cancer cells—allowing them to attack tumors through three pathways simultaneously.
"This cancer is remarkably good at escaping treatment, but it can't escape multiple attack pathways at once," said Dr. Lili Yang, co-senior author and professor at UCLA's Broad Stem Cell Research Center. "By the time it adapts to one threat, our therapy has already hit it from another angle." In mouse models, the therapy achieved complete tumor elimination and prolonged survival compared to conventional CAR-T cell therapies.
The CAR-NKT cells did not trigger graft-versus-host disease in preclinical tests. The scalable process allows production from donated blood stem cells; because NKT cells are naturally compatible with any immune system, a single donation can yield enough cells for thousands of treatments. "The idea is to pre-make the product, cryopreserve it and have it ready to go as soon as the patient needs the therapy," Yang said.
Researchers noted that mesothelin is also present in ovarian, breast, pancreatic, and lung cancers—suggesting broader potential applications for this technology. "This is a platform technology," said Dr. Yanruide (Charlie) Li, co-first author. "The goal is one product that doesn't require patient-by-patient customization." With preclinical studies complete, UCLA plans to submit applications to begin clinical trials.
"Despite its prevalence, endometrial cancer remains understudied," Memarzadeh said. "Research efforts and funding is how that changes. It's what allows us to ask important questions, develop innovative therapies and ultimately get them to the patients who need them." The approach has not yet been tested in humans or approved by federal regulators.
