Expert Insights: CAR T-Cell Therapy Breaking New Ground in Autoimmune Disease

Chimeric antigen receptor T-cell (CAR-T) therapy has shown remarkable success in the fight against blood cancers such as lymphoma, leukemia, and multiple myeloma. Now, CAR-T is making waves in a new arena—autoimmune disease. In fact, many CAR-T researchers and companies have shifted their focus from oncology to autoimmune disease, galvanized by compelling early research studies and a sizable market opportunity.

Expert Insights in AlphaSense is your single-source solution for superior insights on new developments in healthcare and beyond. In this blog, we’ll explore evolving applications of CAR-T therapy and the key industry debates by leveraging first-person insights from the AlphaSense expert transcript library.

Success of CAR-T in Blood Cancer

CAR T-cell therapy started in cancer and has transformed cancer treatment by reengineering patients’ immune systems to fight disease. Specifically, CAR-T therapy involves extracting a patient’s T cells (a type of immune cell), modifying these T cells in a lab so they can recognize and destroy cancer cells, and then reintroducing the re-engineered cells into the patient’s body. 

CAR-T provides a personalized, targeted approach that is different from chemotherapy, which instead targets a wide range of cells, regardless of whether they are cancerous or not.

CAR T-cell therapy process, according to National Cancer Institute.

Approvals of CAR T-cell therapies by the U.S. Food and Drug Administration (FDA) so far have been limited to blood cancers. Novartis was the first to bring a CAR T-cell therapy to the market (in 2017), followed by Gilead, Bristol Myers Squibb, and Johnson & Johnson. These treatments have offered blood cancer patients durable long-term responses and even cures for highly difficult-to-treat conditions.

Less Success in Solid Tumors

Experts said success in blood cancer has prompted CAR-T researchers to expand into therapies for solid cancer tumors. However, experts noted solid tumors are considerably more challenging to treat with CAR-T than liquid tumors (i.e., blood cancers), and progress has been slower than expected.

“People [have been] trying to use CAR-T for solid tumors, and really there isn’t a lot of new progress there in terms of clinical trials or promising data in a preclinical study. That’s a major challenge or a wall that CAR-T just cannot break – it’s a solid tumor. All the good successes [are] really in… blood cancers.”

– Former Cell Therapy Salesperson, Danaher Corp. | Expert Transcript

Experts explain that CAR-T therapy has difficulty targeting solid tumors because solid tumors are composed of many different cell types, each expressing different antigens (which tell the immune system if something in the body is harmful). In contrast, blood cancers are made up of a single cell type that expresses the same antigen.

“With solid tumors, there is the problem of [having a] very, very heterogeneous load of antigens.”

– Associate Medical Director, Oncology, AstraZeneca PLC | Expert Transcript

Experts also said collagen scars create barriers around solid tumors, which are difficult for the disease-attacking T cells to penetrate. Furthermore, experts said any T cells that can penetrate the barrier are often eliminated by immunosuppressive cells and molecules contained within the tumor.

Breakthrough Discovery in Autoimmune Disease

The challenges researchers face in applying CAR-T to solid cancer tumors have created an opening for an exciting new CAR-T application: autoimmune disease.

Autoimmune diseases are chronic conditions that occur when the body’s immune system mistakenly attacks its own healthy tissues, organs, and cells. Autoimmune diseases cause inflammation that can affect any part of the body, and symptoms can range in severity from manageable to life-threatening. Common symptoms include fatigue, fever, muscle aches and weakness, joint pain and swelling, skin problems, abdominal pain and digestion problems. 

In February 2024, a team of German scientists threw a spotlight on the opportunity for CAR-T in autoimmune disease with results from a case series in which fifteen patients (8 with systemic lupus erythematosus, 4 with systemic sclerosis, 3 with myositis) all achieved complete remission after receiving a single infusion of CAR-T therapy.

Prior to CAR-T, these patients had undergone multiple alternative treatments that had failed. These outcomes grabbed the industry’s attention and have drawn widespread acclaim, including that of AlphaSense experts.

“It’s a small sample, but we have people who have these chronic ailments that we tell them there’s no cure [for], and now, in a strange way, we have cured them. … It’s really exciting.”

– Rheumatologist in private practice | Expert Transcript

The study also found that patients, once in remission, were able to stop taking immunosuppressant medications, which can be toxic and cause long-term side effects such as diabetes and hypertension.

“I’m super impressed by the results. It’s pretty amazing. These are chronic immune conditions. …The most impressive part is these patients were on multiple medications, really severe disease activity, and with one treatment of this CAR-T therapy, got off all of their medications, including the steroids.”

– Rheumatologist in private practice | Expert Transcript

Additional Research Supports CAR-T in Autoimmune Disease

The industry is moving quickly to bring CAR-T autoimmune disease therapies to market. For example, as of December 2023, more than 30 companies had announced plans to pursue development in this area, and more than 70 programs were in development, according to William Blair. In addition, as of May 2024, more than 50 clinical trials for autoimmune disease were registered on the National Institute of Health’s clinical trial database, ClinicalTrials.gov, according to B. Riley Securities.

Although most companies have yet to report trial results, experts say recent trial updates from a handful of companies, including Kyverna Therapeutics, Cabaletta Bio, and Novartis, are encouraging and supportive of the German research team’s findings.

For example, at the June 2024 meeting of the European Alliance of Associations for Rheumatology (EULAR), Cabaletta reported that two of its initial CAR-T therapy patients had significant improvements: one is now drug-free, and the other is reducing steroid use.

“It’s a few cases only, [but they] look promising. They look pretty good. …It’s definitely a topic that would evoke interest specifically in patients who are resistant to treatment, patients who are not responding to medications that are generally used for these conditions.”

– Rheumatologist in private practice | Expert Transcript

In another example from the EULAR meeting, Kyverna reported that six of seven lupus patients treated with CAR-T had been able to stop their medications. In addition, a patient with myasthenia gravis is in complete remission, requiring no additional medications for a year following CAR-T treatment.

“[Kyverna’s data] just basically confirms my opinion on CAR T-cell, that it is a good and promising therapy that I am awaiting… to become widely available.”

– Rheumatologist, Cleveland Clinic | Expert Transcript

Still, the news was not all positive at EULAR. It was revealed that one myositis patient who was part of the German study discussed earlier had relapsed after 18 months, while Kyverna reported that one lupus patient treated with its CAR-T therapy had relapsed after five months. Kyverna’s stock took a hit on the news.

Focus on B-Cell Driven Autoimmune Diseases

CAR-T researchers are focusing on a group of autoimmune diseases referred to as B-cell mediated diseases, which include lupus, rheumatoid arthritis, and multiple sclerosis. In this disease group, B cells (a type of white blood cell) in the immune system go haywire and start attacking healthy cells.

These B cells contain a specific protein on their surface that CAR-T can recognize and target. In doing so, CAR-T is able to reduce and even eliminate the bad B cells, resulting in what experts describe as a “reset” of the body’s immune system.

Notably, the B-cell targets employed in autoimmune CAR-T therapy happen to be the same as those employed in CAR-T therapies for blood cancers. However, the side effects appear to be less severe in autoimmune patients, which also drew praise from experts.

“What we’ve seen is that all the autoimmune populations that have been treated so far with CAR-T have had way less side effects than the oncology space.”

– Neurologist, Cleveland Clinic | Expert Transcript

Experts explained that autoimmune disease patients have fewer bad B cells to eliminate than cancer patients, so the CAR-T therapy is less taxing on autoimmune patients.

“In oncology, you see worse [side effects] because the B-cell populations are more out of control in patients with lymphoma, but in patients with autoimmune diseases like lupus or myositis, your B-cell populations are not necessarily higher than what a normal person’s would be. It’s more just that [the B cells in autoimmune diseases are] targeting the wrong thing (healthy cells).”

– Rheumatologist in private practice | Expert Transcript

Large Market Opportunity in Autoimmune Disease

According to the Autoimmune Association, there are over 100 autoimmune conditions affecting more than 50 million Americans. Of those affected, 25% have multiple autoimmune diseases, and approximately 80% of diagnosed patients are women.

Statistics for autoimmune diseases, according to the Autoimmune Association.

In looking at the portion of autoimmune patients who could be CAR-T candidates, Morgan Stanley estimates the global opportunity to be around 8.3 million people living with B-cell driven autoimmune diseases. In financial terms, William Blair estimates the opportunity for CAR-T therapy in autoimmune disease to be $70 billion to $150 billion in the United States alone and could reach $263 billion depending on which autoimmune indications receive approval.

Not surprisingly, the sheer market size of CAR-T autoimmune applications, coupled with the promising early research, has unleashed major deal activity. Piper Sandler estimates 44 deals totaling $8.79B in disclosed value were struck between January 2022 and May 2024.

Completed deals in the autoimmune disease cell therapy space, according to Piper Sandler.

Many of these deals involve large pharmaceutical companies, including acquisitions and partnerships aimed at advancing CAR-T therapies for autoimmune diseases, such as:

• AstraZeneca PLC’s $1.2B purchase of Gracell Biotechnologies in February 2024 and $2.085B agreement with Quell Therapeutics in June 2023 to develop CAR T-cell therapies for autoimmune disease
• Regeneron Pharmaceuticals’ early-2024 acquisition of 2Seventy Bio’s experimental cell therapies and March 2023 partnership with Sonoma Biotherapeutics to co-develop cell therapies for autoimmune disease
• Bristol-Myers Squibb’s August 2022 partnership with GentiBio to develop cell therapies for inflammatory bowel disease; the deal is worth up to $1.9B

In addition, a number of companies developing CAR-T for autoimmune diseases have raised equity in the public markets. Of particular note, Kyverna Therapeutics went public in February and garnered a higher than expected $319M in gross proceeds.

Challenges for CAR-T in Treating Autoimmune Diseases

Amid the enthusiasm, experts have also flagged potential challenges with using CAR-T to treat autoimmune diseases, as discussed below.

Competition with Existing Treatments

Some experts described CAR-T as the treatment of “last resort,” especially in lupus, because several effective treatments already exist for most lupus patients. 

“Do I think that CAR-T therapy will be the first thing that we reach for out-of-the-box? No, particularly for lupus. Despite the common belief that lupus is a death sentence, most lupus is not life-threatening, exempting, obviously, lupus nephritis. We have really great treatments for lupus …I don’t see a whole lot of refractory disease in lupus. That said, obviously, for patients with severe lupus who are refractory… there’s a need, and I think CAR-T would fulfill that.”

– Rheumatologist in private practice | Expert Transcript

Consequently, a rheumatologist with a large academic hospital estimated that just 1%-2% of their lupus patients would be good candidates for CAR-T when it becomes available. However, experts said the opportunity is robust in autoimmune diseases where treatment options are minimal or nonexistent, such as myositis and scleroderma.

Obstacles in Supply and Logistics for CAR-T

Generating and maintaining a sufficient and affordable supply of CAR-T cells is a challenge, according to experts, because CAR-T cells are living cells that must be kept alive, cultured, and expanded.

Today, most CAR-T therapy is autologous, which means the cells come from each individual patient. However, allogeneic (or off-the-shelf) therapy is considered a cheaper and faster alternative because it relies on cells from a single donor that can then be used for multiple patients (similar to blood donation).

Experts suggest progress in developing allogeneic therapies has been slow, given the complexity of addressing the diversity of immune systems across the population, but it is moving in the right direction nonetheless.

“I think it’s been challenging. We’ve seen a number of those companies fail, but I think they’re getting there. …Serving every patient with the huge diversity [in] immune systems… is not going to be easy, but it’s another worthwhile arm to pursue, and I’m hopeful.”

– Former CTO, Pionyr Immunotherapeutics | Expert Transcript

Meanwhile, experts expect CAR-T therapy will be limited to large treatment centers, which is likely to create logistical challenges, particularly for patients who do not live nearby.

“These are obviously going to be done at specialized centers and the patient may need to travel. …It [would] entail the patient leaving your practice and going to a major center, getting treated by people that they really don’t know after establishing a long-term bond with [their] rheumatologist and having to go up and back in and probably hospitalized at that other center for one or two times to go through this process. There are going to be some patients who are going to decline initially because of the commitment in terms of time travel and hospitalization.”

– Rheumatologist in private practice | Expert Transcript

Despite these challenges, the future outlook for CAR-T in treating autoimmune diseases is overall promising as new research developments continue to unfold.

Discover more expert perspectives on healthcare developments in our report, How Artificial Intelligence is Reshaping Drug Development.

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