If CAR-T Proves Able to Effectively and Durably Treat Autoimmune Disease it May Greatly Benefit Lives of Patients

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Bruce Cree, MD, PhD, MAS, a professor of neurology and the clinical research director of the University of California San Francisco (UCSF) Multiple Sclerosis Center discussed the potential impact of CAR-T therapy on the lives of patients with autoimmune disease.

Bruce Cree, MD, PhD, MAS, a professor of neurology and the clinical research director of the University of California San Francisco (UCSF) Multiple Sclerosis Center

Bruce Cree, MD, PhD, MAS

This is the third part of an interview with Bruce Cree, MD, PhD, MAS. For the first part, click here.

Although highly effective treatments for some autoimmune disease indications exist, many patientis with various autoimmune diseases have progressive disease that is refractory to standard of care treatments. As such, great unmet need remains for this subset of patients with autoimmune disease.

Bruce Cree, MD, PhD, MAS, a professor of neurology and the clinical research director of the University of California San Francisco (UCSF) Multiple Sclerosis Center, recently spoke with CGTLive® about how chimeric antigen receptor T-cell (CAR-T) therapies, many of which are currently in clinical development for autoimmune diseases, may provide a new effective treatment option for patients with refractory disease. Although, he noted that rigorous randomized-control clinical trials are needed to establish efficacy and that the very high costs of producing individalized therapies like CAR-T need to be considered.

CGTLive: What potential do you see CAR T-cell therapy having in changing the lives of patients with autoimmune diseases?

Bruce Cree, MD, PhD, MAS: There is a very significant unmet need for treatments that work extremely well and are safe and well-tolerated in autoimmune disease in general. Now, we have some very good therapies that are out there for certain autoimmune diseases. I would say for example, with rheumatoid arthritis, we have fantastic therapies that work extremely well and are an incredible step forward compared to the old treatments that we used to use like methotrexate and leflunomide. We've made huge progress in treatment of rheumatoid arthritis.

But there are other conditions that are life-threatening autoimmune diseases or severely disabling autoimmune diseases for which we don't have great treatment options. So there's clearly an unmet need in many autoimmune diseases—I include progressive forms of multiple sclerosis that are treatment-refractory in that setting—and that's, of course, my main interest.

If we develop therapies that have a substantial effect in patients who aren't responding well to our standard of care treatments, we're of course going to be benefiting lives, right? These therapies have the potential to be highly durable: You get treated with the CAR-T therapy once, these are your own cells and they stick around potentially for many years, and they have the potential to be reactivated and reexpanded later when you need them. A durable therapeutic treatment, even if you have to go through immunodepletion to get there, could have a profound effect that's beneficial for many patients lives.

Do we know that we're going to get there with CAR-T therapy? No. We're just at the start of all of this and we have some encouraging open-label, uncontrolled pieces of evidence that are absolutely tantalizing. Absolutely, this deserves further investigation. But we absolutely cannot simply embrace this as a panacea for autoimmune disease. We have to be willing to roll up our sleeves and do the hard work of randomized, well-constructed, carefully-designed clinical trials that will provide unambiguous evidence of efficacy. That is the key thing. So as exciting as this is, we've got to be willing to roll up our sleeves and do the work.

These therapies are going to be expensive therapies, too. These are treatments that are individual immune therapy treatments and they involve a lot of technology and a lot of work. Basically, what you're doing is you're making a drug for each person who ever gets treated. That has certain advantages, potentially, right? It's your own therapy. But there is certainly a big disadvantage in the sense that if you're going to construct something on an “n = 1” scale, it's going to be very expensive. Think about it. If you're going to build a car for 1 person from scratch, it's going to cost you a whole lot more to build that 1 car than if you're going to take the same car and build a million of them. It's a question of economy of scale. Because we do know that there is going to be a significant price associated with this, the reward must be high as well. If we can cure—that’s a great word to use—or effectively treat autoimmune disease with a durable/consistent effect with CAR-T therapy, this is going to be a major step for medicine and will be of great benefit to many patients.

This transcript has been edited for clarity.

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