CAR-T Therapy for Autoimmune Diseases
A guide for the novice
Welcome to this newsletter! If you’re new to CAR-T therapy, this guide will introduce you to an exciting medical breakthrough that’s making waves in treating autoimmune diseases. Originally developed for cancer, (chimeric antigen receptor T-cell) CAR-T therapy is now showing promise for conditions like lupus and multiple sclerosis, where the immune system attacks the body. Inspired by recent moves like AbbVie’s acquisition of Capstan Therapeutics, we’ll explore what CAR-T is, who’s leading the charge, the challenges ahead, and why this matters—all in clear, college-level language.
Introduction to CAR-T Therapy
What Is CAR-T Therapy?
CAR-T (Chimeric Antigen Receptor T-cell) therapy is a revolutionary treatment that reprograms your immune system to fight disease. Doctors take T cells (immune cells that act like soldiers) from your blood, modify them in a lab to recognize harmful cells, and then put them back into your body. These upgraded T cells hunt down and destroy the target cells, like a guided missile. The graphic below shows the steps in the autologous (using the patient’s own blood cells) CAR-T
From Cancer to Autoimmune Diseases
CAR-T therapy first gained fame for treating blood cancers, helping some patients achieve complete remission. Now, researchers are using it to tackle autoimmune diseases—conditions where the immune system mistakenly attacks healthy tissues, like in systemic lupus erythematosus (SLE), myasthenia gravis, or systemic sclerosis. The goal is to “reset” the immune system, potentially offering long-term relief without constant medications.
Why This Is Exciting
For people with severe autoimmune diseases who don’t respond to standard drugs, CAR-T could be a lifeline. A single treatment might stop the disease for years, reducing the need for daily pills or infusions. The recent acquisition of Capstan Therapeutics by AbbVie shows that big pharmaceutical companies are betting on this technology, signaling a bright future.
The Competitive Landscape: Who’s Making It Happen?
The field of CAR-T therapy for autoimmune diseases is growing fast, with companies and universities working together to develop new treatments. Here’s a look at the key players, their approaches, and the latest progress.
Emerging Clinical Evidence
A Surge in Research
Research is booming, with over 50 clinical trials worldwide exploring CAR-T for autoimmune diseases. A 2024 study by Zhou et al. in the New England Journal of Medicine showed that 15 patients with lupus, myositis, or systemic sclerosis had major improvements after a single CAR-T treatment. Lupus patients achieved full remission, and no relapses were seen up to two years later.
Diseases and Trials
Here’s a quick overview of the research scope:
Disease Number of Ongoing Trials Systemic Lupus Erythematosus (SLE) ~20 Myasthenia Gravis ~10 Systemic Sclerosis ~8 Idiopathic Inflammatory Myositis ~7 Multiple Sclerosis ~5
This table shows how CAR-T is being tested across a range of autoimmune conditions, with lupus leading the way.
Key Players and Programs
Bristol Myers Squibb (BMS)
BMS, a leader in cancer CAR-T therapies like Breyanzi, is developing CD19 NEX-T, which targets B cells (immune cells that drive many autoimmune diseases). They’re testing it for severe conditions, with results expected in 2025.
Kyverna Therapeutics
Kyverna’s KYV-101 is a CAR-T therapy designed to minimize side effects like immune overreactions. It’s being studied for stiff person syndrome, myasthenia gravis, and lupus nephritis, with plans to seek FDA approval for some conditions by 2025.
CRISPR Therapeutics
Using their gene-editing expertise, CRISPR Therapeutics is working on CTX112, an “off-the-shelf” CAR-T therapy that doesn’t need to be customized for each patient. This could make treatment faster and more accessible, and they’re testing it for various autoimmune diseases.
Cabaletta Bio
Cabaletta’s CABA-201 targets B cells for lupus and related conditions. They’re running trials at places like UC Davis Health to evaluate its effectiveness.
Academic Pioneers
Universities are driving innovation too. The University of Chicago Medicine and Germany’s University of Erlangen-Nuremberg are running early trials on CAR-T therapies for lupus, systemic sclerosis, and myositis, exploring new ways to target the immune system.
Innovative Approaches
Off-the-Shelf CAR-T
Traditional CAR-T uses a patient’s own cells, which takes time to prepare. Allogeneic (off-the-shelf) CAR-T, being developed by companies like Allogene Therapeutics, uses donor cells that can be pre-made, making treatment quicker and potentially cheaper.
New Targets
Most CAR-T therapies target B cells via a marker called CD19, but researchers are exploring other targets like BCMA (on plasma cells) or fibroblast-activated protein. This could help treat more types of autoimmune diseases.
Regulatory T Cells (Tregs)
Instead of destroying harmful cells, CAR-Tregs are designed to calm the immune system. This could be a gentler approach for diseases like multiple sclerosis, where immune balance is key.
Temporary CAR-T
Using mRNA, researchers are creating CAR-T cells that work temporarily and then fade away. This avoids permanent changes to your DNA, potentially reducing risks like secondary cancers.
Challenges Facing CAR-T Therapy
While CAR-T therapy is promising, it faces several hurdles that need to be addressed before it can become a standard treatment. Here’s what’s standing in the way.
Efficacy and Long-Term Outcomes
Will It Last?
Early trials show patients staying symptom-free for years, but we don’t know if this will continue long-term. If B cells return, the disease might come back, so researchers are studying how to make remission last.
Lack of Control Groups
It’s hard to prove CAR-T works better than other treatments because trials often don’t include placebo groups (for ethical reasons, since these diseases can be severe). This makes it tricky to confirm that improvements are due to CAR-T alone.
Safety Concerns
Cytokine Release Syndrome (CRS)
CAR-T can cause CRS, where the immune system overreacts, leading to fever or fatigue. In autoimmune trials, CRS is usually mild and resolves within ~15 days, but it still needs careful monitoring.
Neurotoxicity
Some patients experience brain-related side effects (called ICANS), though these are rare in autoimmune trials. Doctors are working to minimize this risk.
Infection Risks
CAR-T often requires drugs that weaken the immune system temporarily, increasing infection risk. About 25% of trial patients had infections, so vaccinations and follow-up care are crucial.
Long-Term Effects
Some patients lose B cells (25–38%) or antibodies (18–74%) for a long time, which can weaken immunity. There’s also a small risk of late complications, like new cancers, requiring long-term monitoring.
Conditioning Therapy
Many CAR-T treatments need “conditioning” drugs (like chemotherapy) to prepare the body, which adds risks like nausea or hair loss.
Manufacturing and Cost
Complex Process
Making CAR-T cells is complicated. Doctors collect your T cells, modify them in a lab, and return them for infusion. This takes weeks and costs $375,000–$425,000 per treatment in the U.S.
Time Delays
The long manufacturing process can delay treatment, which is a problem for patients with fast-progressing diseases. Off-the-shelf CAR-T could help solve this.
Specialized Centers
CAR-T requires hospitals with trained staff and special equipment, which aren’t available everywhere, limiting access.
Regulatory Hurdles
The FDA requires strict safety plans (called REMS) for CAR-T, adding complexity to getting treatments approved and distributed.
Patient Selection and Disease Heterogeneity
Who’s the Right Fit?
Not all patients benefit from CAR-T. It’s best for those with severe, treatment-resistant diseases and minimal organ damage. Figuring out who qualifies is tough because autoimmune diseases vary widely.
Choosing Targets
Picking the right immune cells to target (like B cells or plasma cells) is challenging. Each disease may need a different approach, and researchers are still learning what works best.
Long-Term Efficacy and Relapse
Immune Reset or Temporary Fix?
We don’t know if CAR-T truly cures autoimmune diseases or just pauses them. If the immune system “reboots” with the same problems, patients might need more treatment.
Comparing to Other Treatments
CAR-T needs to prove it’s better than existing drugs like rituximab (which also targets B cells) or cyclophosphamide. The risks of CAR-T must be worth the benefits.
Additional Therapies
If CAR-T doesn’t fully work, it’s unclear if other immune-suppressing drugs are safe to use afterward, since CAR-T alters the immune system significantly.
Finding Enough Patients
For rare diseases, recruiting enough patients for large trials is hard, slowing down research.
The Path Forward: Overcoming Challenges
Researchers are tackling these hurdles with innovative solutions to make CAR-T safer, cheaper, and more effective.
Improving Safety
Smart CAR-T Designs: Adding “on/off” switches to CAR-T cells could control side effects.
Temporary CAR-T: mRNA-based therapies that don’t permanently change DNA could reduce long-term risks.
Streamlining Manufacturing
Automation: New tech could make CAR-T production faster and less expensive.
Off-the-Shelf CAR-T: Pre-made therapies could cut wait times and costs.
Expanding Uses
New Targets: Targeting BCMA, CD138, or other markers could help more diseases.
Gentler Options: CAR-Tregs might offer a safer way to balance the immune system.
Better Trials
Larger Studies: More patients in trials will clarify how well CAR-T works.
Global Data Sharing: International registries are pooling data to speed up progress.
Reducing Costs
Scalable Solutions: Cheaper manufacturing could make CAR-T more affordable, especially if it saves patients from years of costly drugs.
Why CAR-T Matters
CAR-T therapy could transform how we treat autoimmune diseases, offering hope to patients who’ve run out of options. Early trials show people with lupus and other conditions living symptom-free after one treatment, a huge leap from lifelong medications. With big players like AbbVie investing in companies like Capstan Therapeutics, and universities pushing new ideas, CAR-T could become a standard treatment in the coming years. Overcoming challenges like safety, cost, and access will be key to making this a reality for more people.
Get Involved!
Are you curious about CAR-T therapy or working in healthcare? Share your thoughts in the comments—what do you find exciting or want to learn more about? Let’s connect to discuss how CAR-T could change lives. Subscribe to this newsletter for more beginner-friendly updates on cutting-edge medical advances!
Sources: New England Journal of Medicine (2024), Nature Reviews Rheumatology, BioSpace.