UCLA research team awarded millions to bring new MS therapy to trial
State funding drives development of off-the-shelf, cell-based treatment
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Millions of dollars in state grant money will help advance a new cell therapy for MS toward its first human trial. (Image from iStock)
- A UCLA research team was awarded a $7.49M grant to advance a novel cell therapy for multiple sclerosis.
- This CAR-NKT cell therapy targets B-cells and inflammation, aiming for long-lasting control of MS.
- The new funding will help bring the treatment candidate to its first human trials.
A research team at the University of California, Los Angeles (UCLA) has received a $7.49 million grant to advance a novel cell-based therapy for multiple sclerosis (MS) toward its first clinical trial.
The state funding, awarded by the California Institute for Regenerative Medicine (CIRM), was earmarked for a team led by Lili Yang, PhD, a professor and the researcher behind the Yang Engineering Immunity Lab at UCLA.
The team’s new off-the-shelf treatment candidate uses specialized immune cells — called natural killer T-cells or NKT cells — engineered in the lab to halt both the abnormal immune attacks and the chronic inflammation that drive MS. These cells can help reset the immune system and remain in the body for months to years, so the researchers hope a single dose could provide long-lasting disease control.
“With this approach, we hope to achieve a much more significant delay — or even a cure,” Yang said in a university news story announcing the grant from CIRM, a state agency created by California voters to advance treatments for diseases with unmet need.
“If we can truly reset the immune system, we may be able to keep another serious attack at bay indefinitely,” Yang said.
The new funding will support the development of this off-the-shelf, or readily available, immunotherapy treatment for MS.
MS occurs when the immune system mistakenly attacks healthy tissue in the brain and spinal cord, collectively known as the central nervous system (CNS). This triggers inflammation that gradually damages nerve cells.
Current approved MS treatments can generally suppress the acute immune attacks that trigger MS relapses, but they do little to stop the chronic inflammation that drives ongoing nerve damage and gradual disability worsening.
Researchers develop new approach to CAR T-cell therapy
One promising approach is CAR T-cell therapy, which turns a patient’s own T-cells — immune cells that normally help defend the body against infections — into disease fighters. Traditionally, the approach works by collecting T-cells and genetically engineering them in the lab to produce a man-made receptor, called a chimeric antigen receptor, or CAR, that targets disease-causing cells.
In MS and other autoimmune diseases, researchers have been testing CAR T-cells that recognize and destroy B-cells, immune cells that contribute to the harmful autoimmune attacks in MS.
Now, Yang and her team are taking that strategy a step further by building on a CAR-NKT cell therapy platform that her lab has spent more than a decade developing to fight cancer. Rather than engineering T-cells, the platform uses NKT cells.
Like CAR T-cell therapies, the engineered CAR-NKT cells are designed to seek out and destroy B-cells. But the NKT cells have another important characteristic that T-cells lack: their natural ability to recognize and attack myeloid cells, immune cells that accumulate in the brain and spinal cord and help sustain the chronic inflammation that drives ongoing nerve damage.
Regular CAR-T cells will wipe out the bad B cells, and we can do the same — but we do more than that. … CAR-NKT cells … work on two fronts.
By targeting both B-cells and inflammatory myeloid cells at the same time, the therapy is designed to tackle two major drivers of disease, according to the researchers.
“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, also a 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,” Yang noted, adding, “They work on two fronts. That’s very important for dealing with this disease.”
Yang and her team believe this strategy could provide longer-lasting disease control than current medications. Because CAR-NKT cells can persist in the body for months or even years, and it takes time for newly formed B-cells to become capable of triggering autoimmune attacks, one treatment course could be enough to reset the immune system — though additional doses may be given, if needed.
Cost of this off-the-shelf MS therapy could be as low as $5K
Unlike conventional CAR T-cell therapies, which are custom-made for each patient and expensive to produce, CAR-NKT cells can be manufactured in advance from umbilical cord blood. They can then be frozen and stored until needed.
According to the researchers, a single cord blood donation could yield enough cells to produce thousands of treatment doses.
“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.”
In an established mouse model of MS, CAR-NKT cell treatment has already shown encouraging results by preventing mice from developing paralysis.
“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 team also met with the U.S. Food and Drug Administration in a pre-investigational new drug (IND) meeting to discuss the path toward human testing. Over the next 2.5 years, the scientists plan to manufacture a clinical-grade version of the therapy, produce hundreds of treatment doses, and seek IND clearance, which would allow clinical trials to begin.
If successful, the platform could also be adapted to treat other autoimmune diseases, including lupus and rheumatoid arthritis, according to Yang.
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