CAR T cell therapy for autoimmune disease gains traction

Cell therapies for autoimmune diseases were a hot topic at The American College of Rheumatology’s (ACR) Convergence 2024 meeting this past November. In 2021, scientist Georg Schett and his team at Friedrich-Alexander-University Erlangen-Nuremberg published early positive results using chimeric antigen receptor (CAR) T cell therapy to treat a severe case of lupus (1). Now, CAR T cell therapy development for lupus and other autoimmune diseases is in full swing with companies testing new therapies in all aspects of the development pipeline — from preclinical and manufacturability studies to human clinical trials.

At the recent meeting, Schett — in collaboration with researchers from Bristol-Myers Squibb (BMS) — presented the first data from their Phase 1 clinical trial for their CAR T cell therapy in patients with one of three severe autoimmune diseases: systemic lupus erythematosus, systemic sclerosis, or idiopathic inflammatory myopathy (2).

Tim Campbell, the Vice President of Hematology and Cell Therapy, Early Clinical Development at BMS, explained that while these conditions significantly affect patients’ organ function, “they also really impact quality of life for patients … the ability of these patients to have normal work life, normal family planning, and other issues long term.”

A successful CAR T cell-based treatment would reset a patient’s immune system, allowing them to halt immunosuppressive treatments and go into remission. Campbell spoke with DDN about how he and the BMS team are hopeful that their CAR T cell therapy will do just that.

How did BMS get interested in developing a CAR T cell therapy for autoimmune diseases?

We had seen a lot of academic and industry interest in the potential of CD19 CAR T cells having a transformational effect in patients with severe autoimmune diseases. Because BMS is a leader in cell therapy, it's a very natural area for us to go into and potentially develop a transformational therapy for these patients. Additionally, the current treatments for some of these severe autoimmune diseases really focus on reducing symptoms, and patients often must take them long term to try to keep the immune system under constant pressure. We really feel like patients need novel therapies — a one-time infusion that has the potential to transform their underlying disease.

Tim Campbell leads the Hematology and Cell Therapy, Early Clinical Development at BMS.

Credit: Bristol Myers Squibb

Can you tell me more about your CAR T cell therapy?

This product, CC-97540 (BMS-986353), has the same CD19 construct as Breyanzi, which is BMS’s Food and Drug Administration approved CD19 CAR T therapy for adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). However, its manufacturing process is shorter. Compared to the traditional CAR T cell expansion processes, in this manufacturing process — called NEX-T — the CAR T cells are minimally expanded, so the whole process has a faster turnaround time. Also, this manufacturing process tends to create a drug product that is potent and can expand well in patients.

What are the results of your Phase 1 trial so far?

This is our first data disclosure highlighting the safety and efficacy in 11 patients with lupus, three patients with scleroderma, and one patient with inflammatory myositis. If we look just at the patients with lupus, which represent the biggest number of patients that we've treated so far with the longest follow up, we're seeing what I would say are transformational efficacy results. Our patients are coming off of immunosuppressive medications. We're seeing significant reductions in their disease activity scores, and patients are not requiring any immunosuppression for more than 11 months. The therapy is really having transformational effects on patients’ quality of life.

In terms of safety, in the whole 15-patient group we're seeing nothing unexpected. All instances of cytokine release syndrome have been low grade, either grade one or two, and all of the inflammatory toxicities have been manageable and transient. So, we're seeing an early but reassuring profile for these patients with severe autoimmune diseases. We also see early signs of immune reset, which is consistent with what others have seen in academic and industry studies. We're really excited about continuing the development of this asset.

How did it feel to see these positive results?

The current approaches for these patients are often to stay on multiple drugs for many years to try to control their underlying inflammation. Now, we have these therapies that potentially offer a one-time treatment that allow patients to get off of those medicines and remain in sustained remission. It's early days for these data across the board in academia and industry, but I think we're really starting to realize the potential of these cell therapies in severe autoimmune disease. For me, personally, as a physician working in industry and hearing stories about patients being able to go back to work or living without debilitating symptoms is incredibly reassuring and positive.

For me, personally, as a physician working in industry and hearing stories about patients being able to go back to work or living without debilitating symptoms is incredibly reassuring and positive.
- Tim Campbell, Bristol Myers Squibb

What’s next for this CAR T cell therapy?

We're really excited about this first data disclosure, and we look forward to future data disclosures from this same trial. We also have a separate Phase 1 trial enrolling multiple sclerosis patients with the same asset, CD19 NEX-T, and we're really excited to see some of those data also mature and have our first data disclosure on that trial, hopefully soon.

What has working on this project meant to you as a scientist?

I've been working in cell therapy for my entire career at BMS and prior to that, starting at Celgene, which was acquired by BMS. I worked on myeloma CAR T cell therapy, and I saw transformational responses in patients. They lived longer and healthier lives in myeloma-free states, and I think when these assets go into new populations, we will start to see those similar types of transformational clinical results. It's the best thing that you can ask for. For me, that's by far the most rewarding part.