CAR-T cell therapy for multiple sclerosis is currently one of the most discussed and promising developments in neuroimmunology—and at the same time one of the most complex and least understood. In this in-depth conversation, neurologist and researcher Professor Barbara Willekens explains where the science truly stands today, what we know from early data, and why both optimism and caution are equally justified.
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1. Introduction & Personal Background
Barbara, it’s great to have you back on the podcast! For those who don’t know you yet – could you briefly introduce yourself?
Professor Barbara Willekens (Neurologist, University of Antwerp):
I am a neurologist and researcher working in Antwerp, Belgium, focusing on multiple sclerosis and other neuroimmune disorders. My work centers on improving treatment options for people with MS. One of my main interests, already since my PhD, is cell-based therapies, including tolerogenic dendritic cell treatments. These approaches aim to modulate the immune system more precisely.
If you’d like to learn more about Professor Willekens’ work on brain health in MS, you can listen to our previous conversation on the MS Brain Health Strategy (Episode 125).
CAR-T cell therapy is gaining attention in the MS field – what sparked your personal or professional interest in this topic?
Professor Barbara Willekens:
CAR-T cell therapy has been developed over more than 30 years, mainly in hematological malignancies (blood cancers). In that field, it has dramatically changed outcomes, even leading to cures in patients who had no remaining treatment options.
The connection to MS lies in the role of B cells. In both blood cancers and multiple sclerosis, B cells play a key role. In MS, they contribute to ongoing disease activity. That is why CAR-T therapy, which targets B cells, is now being explored for autoimmune diseases.
2. Understanding CAR-T Cell Therapy
What exactly is CAR-T cell therapy – and how does it work inside the body?
Professor Barbara Willekens:
CAR-T cells are usually produced using the patient’s own immune cells, a process called autologous therapy.
The procedure works as follows:
- Blood is collected via leukapheresis (a method to isolate white blood cells).
- These cells are transported to a specialized laboratory.
- There, they are genetically modified to express a chimeric antigen receptor (CAR).
- This receptor allows the cells to recognize specific targets.
- The modified cells are expanded and then reinfused into the patient.
To explain the mechanism in a simple analogy:
A CAR-T cell behaves like Pac-Man—it searches for its target, binds to it, and destroys it.
In MS, the target is typically B cells. However:
➡️ Not only disease-causing B cells are removed, but all B cells expressing the targeted antigen.
How does this approach differ from existing MS therapies?
Professor Barbara Willekens:
Current B-cell therapies, such as monoclonal antibodies, have limited ability to penetrate:
- the brain
- the lymph nodes
CAR-T cells, in contrast:
- are living cells
- can migrate into tissues
- reach the central nervous system
This allows for:
➡️ deep and rapid depletion of B cells within tissues
This is important because it may lead to may lead to what is often referred to as an “immune reset,” although this concept is still under investigation.
Could you walk us through how the therapy is actually carried out – from cell collection to reinfusion and aftercare?
Professor Barbara Willekens:
After reinfusion, patients are closely monitored due to potential immune reactions and changes in blood counts.
Typical course:
- Hospital stay: approximately 2 weeks
- Close monitoring for:
- immune reactions
- infection risk
- After discharge:
- patients must stay close to the hospital for about one month
- frequent follow-ups initially
- later reduced to quarterly visits
Long-term monitoring is essential because this is still a new therapy, and long-term outcomes are not yet fully known.
3. Who Might Benefit – and Who Might Not?
For which patients could CAR-T cell therapy realistically be an option – and why is it not suitable for most people with MS at this stage?
Professor Barbara Willekens:
CAR-T therapy for MS is still in early clinical development (Phase I trials).
Currently:
- Only case reports and small case series exist
- Trials focus primarily on safety
Participants are typically:
➡️ patients with MS who have failed high-efficacy treatments
This means:
➡️ It is not a broadly available treatment and not suitable for most patients at this time
Estimated timeline:
➡️ likely still 10–15 years before wider availability
How does this approach compare to autologous stem cell transplantation – and how can patients weigh the pros and cons of each?
Professor Barbara Willekens:
Both therapies:
- require chemotherapy beforehand
- aim to reset the immune system
Differences:
- Stem cell transplantation:
- broader immune suppression
- more intensive chemotherapy
- CAR-T therapy:
- more targeted approach (B cells)
- less intensive pre-treatment
However:
➡️ There are no direct comparative studies in MS
4. Risks, Hopes & Scientific Status
What are the main risks and uncertainties we’re dealing with today?
Professor Barbara Willekens:
Two major risks known from cancer treatment:
Cytokine Release Syndrome (CRS)
- caused by large release of cytokines (immune signaling proteins)
- symptoms:
- fever
- headache
- muscle pain
ICANS (immune-related neurotoxicity)
- neurological symptoms:
- cognitive impairment
- speech difficulties
Severe cases in cancer patients can lead to ICU admission and, rarely, death.
Important for MS:
➡️ So far, no severe or fatal cases have been reported in MS or autoimmune disease cohorts, although data is still very limited.
A likely explanation is that cancer patients have a higher number of target cells, leading to stronger immune reactions.
Large real-world analyses from U.S. registries such as the CIBMTR (Center for International Blood and Marrow Transplant Research) suggest higher rates of severe cytokine release syndrome and neurotoxicity in patients with hematological malignancies, although direct applicability to autoimmune diseases such as MS remains uncertain. In parallel, translational studies such as DiLillo et al. (Blood Advances, 2021) provide important insights into CAR-T cell activity and immune engagement mechanisms.
What potential benefits do researchers hope CAR-T therapy could offer for MS?
Professor Barbara Willekens:
The main hope is based on results in lupus, a systemic autoimmune disease.
A landmark study by Mackensen et al. (Nature Medicine, 2022) demonstrated that anti-CD19 CAR-T cell therapy induced drug-free remission in a small cohort of patients with severe, treatment-refractory systemic lupus erythematosus..
In early studies:
- patients with no remaining treatment options improved significantly
- other medications could be reduced
- stability was maintained for some time
➡️ This triggered interest in MS
The central concept:
- one-time treatment
- deep B-cell depletion across the body
- immune system rebuild
Goal:
➡️ long-term remission without continuous therapy
However:
➡️ Duration of effect remains unknown
Safety data from oncology, including large registry analyses, provide important insights into potential risks, although transferability to MS remains under investigation.
What do we currently know from early MS studies or from CAR-T use in other diseases like cancer?
Professor Barbara Willekens:
- Early MS data is limited
- Some publications from:
- Europe
- China
- USA
Important variable:
➡️ The target of the CAR receptor
Different targets may:
- affect different B-cell populations
- influence safety and effectiveness
This is still under investigation.
5. Global Research & Access
Where are clinical trials currently taking place, and how can interested patients find and access them?
Professor Barbara Willekens:
Trials are ongoing in:
- United States
- Europe
- United Kingdom
- China
- Australia
Patients can:
- discuss options with their neurologist
- search databases such as
👉 clinicaltrials.gov
What should patients know about eligibility and the practical realities of joining a CAR-T trial?
Professor Barbara Willekens:
Participation depends on strict:
- inclusion criteria
- exclusion criteria
Patients must:
- meet specific clinical requirements
- often have highly active disease
6. Looking Ahead
If CAR-T cell therapy proves effective, how might it be integrated into MS care in the future – in terms of availability, cost, and infrastructure?
Professor Barbara Willekens:
Current approach:
- centralized manufacturing
- highly specialized centers
Future developments may include:
- decentralized production
- off-the-shelf (allogeneic) CAR-T cells
- in vivo CAR-T generation (cells engineered inside the body)
Even in the future:
➡️ Treatment will likely remain limited to specialized referral centers
When you look at the current research into CAR-T cell therapy: What gives you hope – and what makes you cautious?
Professor Barbara Willekens:
Hope:
- rapid global research progress
- improved targeting strategies
- development of highly specific CAR-T cells
Goal:
➡️ targeting only disease-causing B cells (“magic bullet”)
Caution:
- unknown long-term effects
- possible disease recurrence
- unclear retreatment strategies
- high costs
However:
- costs may decrease over time
- long-term remission could offset initial costs
Finally, what message would you like to leave with our listeners?
Professor Barbara Willekens:
The MS field is evolving. There is hope for better and newer treatments. The research community is working hard to improve the lives of people with MS.
Further Resources:
See you soon and try to make the best out of your life,
Nele
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