UCLA Team Awarded $7.49 Million CIRM Grant to Develop Off-the-Shelf CAR-NKT Cell Therapy for Multiple Sclerosis
核心洞察
UCLA researchers led by Lili Yang received a $7.49 million CIRM grant to develop a universal CAR-NKT cell immunotherapy targeting multiple sclerosis (搜索).
The dual-action therapy targets CD19 (搜索)-expressing B cells and inflammatory myeloid cells, addressing two key drivers of MS pathology simultaneously.
Unlike patient-specific CAR-T therapies, the off-the-shelf platform uses cord blood-derived NKT cells, with estimated production costs as low as $5,000 per dose.
A team of UCLA researchers led by Lili Yang has secured a $7.49 million grant from the California Institute for Regenerative Medicine (搜索) (CIRM) to advance a universal chimeric antigen receptor natural killer T (CAR-NKT) cell immunotherapy for multiple sclerosis (搜索) (MS), a chronic autoimmune disease that affects nearly one million adults in the United States and generates an estimated $100 billion annually in national healthcare costs.
The funding aims to propel a novel cell-based approach into clinical trials, addressing what Yang describes as fundamental gaps in the current MS treatment landscape. Despite more than 20 FDA-approved therapies, MS remains incurable, and existing treatments must be taken for life, provide incomplete protection against disability progression, and fail to address the chronic inflammation within the central nervous system (CNS) that drives the most severe forms of the disease. No cell-based immunotherapies are currently approved for MS.
A Dual-Front Mechanism of Action
The therapeutic platform builds on CAR-NKT cell technology that Yang's lab has refined over more than a decade, initially developed for oncology applications. For MS, the team engineers natural killer T cells with a chimeric antigen receptor (CAR) that targets CD19 (搜索), a protein expressed on the surface of B cells — the immune cells responsible for producing autoreactive antibodies that attack the nervous system in MS patients.
Critically, the engineered cells retain their natural receptor, which recognizes and attacks inflammatory myeloid cells such as macrophages that accumulate at sites of CNS damage and are major drivers of disease progression.
"Regular CAR-T cells will wipe out the bad B cells, and we can do the same — but we do more than that," said Yang, a professor of microbiology, immunology and molecular genetics and member of the UCLA Broad Stem Cell Research Center. "The CAR-NKT cells can also use their natural receptor to attack the inflammatory myeloid cells that are causing so much of the CNS damage. They work on two fronts. That's very important for dealing with this disease."
A Living Drug with Durable Effect
Because CAR-NKT cells persist in the body as a "living drug" for months to years, they offer a sustained therapeutic effect that daily or weekly medications cannot match. Furthermore, since new B cells produced by the bone marrow take a long time to become autoreactive, a single treatment course may be sufficient to reset the disease clock, with redosing possible if needed.
"With this approach, we hope to achieve a much more significant delay — or even a cure," said Yang, who is also a member of the UCLA Health Jonsson Comprehensive Cancer Center. "If we can truly reset the immune system, we may be able to keep another serious attack at bay indefinitely."
Off-the-Shelf Accessibility and Cost Advantages
One of the platform's most significant advantages is its universal, off-the-shelf design. Traditional cellular immunotherapies are manufactured individually for each patient — a process that can take weeks and cost hundreds of thousands of dollars. In contrast, NKT cells are naturally compatible with any patient's immune system, enabling large-batch production from donated cord blood stem cells. A single cord blood donation can yield enough cells for thousands of doses, which can be frozen and made ready for immediate use.
"We estimate the cost to produce one dose could be as low as $5,000," Yang said. "And those cells are universal — we don't need to customize them for each individual patient. They're made. They're ready."
Preclinical Validation and Regulatory Progress
The team has already generated encouraging evidence in an established preclinical model of human MS, in which mice develop paralysis through the same immune-mediated mechanism that damages the CNS in patients. CAR-NKT cell treatment clearly prevented that outcome.
"It's not just a cellular or molecular readout," Yang said. "It's a real, actual benefit we see in mouse models of the disease."
The researchers have also completed a successful pre-IND meeting with the FDA, which provided clear guidance on the steps required to advance to a clinical trial. Manufacturing will be carried out in UCLA's Center for Advanced Biotherapies, which has validated processes for producing stem cell-derived immune cell products.
By the end of the 2.5-year grant period, Yang and her collaborators aim to have an IND clearance in hand, a clinical-grade product ready for patients, and at least hundreds of doses manufactured.
The Collaborative Team and Future Horizons
Yang is joined on the project by Sarah Larson, a clinician specializing in CAR-T cell therapy clinical trials who has collaborated with Yang for years on blood malignancies, and Eric Williamson, a neurologist specializing in MS patient care who will lead the development of the clinical protocol.
If the therapy proves effective for MS, Yang sees a clear path to other autoimmune conditions driven by autoreactive antibodies, including systemic lupus erythematosus (搜索) and rheumatoid arthritis (搜索). Because the team plans to manufacture hundreds to thousands of doses, clinical testing in additional disease indications could begin without a separate manufacturing campaign.
The MS grant is the latest in a series of CIRM-funded efforts to advance Yang's CAR-NKT platform across a range of diseases. Her lab is also developing CAR-NKT cell therapies for cancers including those of the breast, prostate, ovaries, and pancreas.
"That's what we are really excited about," Yang said. "The fundamental reason we designed this platform from the beginning was to help as many people — and address as many medical needs — as possible."