ECTRIMS 2025 | The expansion of CAR T-cells into the bloodstream of patients with MS: insights from a Phase I trial
Jeffrey Dunn, MD, Stanford University School of Medicine, Palo Alto, CA, shares findings related to the expansion of CAR T-cells into the bloodstream of patients with multiple sclerosis (MS) from a Phase I trial (NCT06138132). Prof. Dunn highlights that the infused CAR T-cells successfully expanded in the patients’ blood and penetrated the central nervous system, as evidenced by their presence in the cerebrospinal fluid of all treated subjects. This interview took place at the 41st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Barcelona, Spain.
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Transcript
We had unanswered questions. Not just, could we do this? The answer is, it seems to be yes. But do the CAR T-cells that are infused at that baseline level, do they successfully expand? Do they expand in the patient’s blood? And then maybe more importantly, do they penetrate and access the central nervous system? And there’s a reason to think that’s critically important for successful treatment of MS, which I’ll mention in a bit...
We had unanswered questions. Not just, could we do this? The answer is, it seems to be yes. But do the CAR T-cells that are infused at that baseline level, do they successfully expand? Do they expand in the patient’s blood? And then maybe more importantly, do they penetrate and access the central nervous system? And there’s a reason to think that’s critically important for successful treatment of MS, which I’ll mention in a bit. So we did very significant testing of blood with multiple blood draws from day zero, the day of infusion, to day 28, which is the time at which we know CAR T-cells generally have done their business and then moved on. And we also did serial spinal taps. Again, a shout out to the subjects and their bravery for willing to step up and volunteer to do three or sometimes four serial lumbar punctures. So we looked at their cerebrospinal fluid that we obtained by spinal tap at baseline prior to the time that they were treated. And then we looked again at day 14, two weeks after their infusion, to see if the CAR T-cells we had infused into their bloodstream had successfully gotten into their cerebrospinal fluid. We looked again at six months to see if there was any immune impact that we could see, such as in a decrease in oligoclonal bands, which is the signature of the antibodies that can collect inside the central nervous system, and in a sense is a hallmark of the pathophysiology of multiple sclerosis. That was key. So those data were very encouraging. What we saw was after infusion, as I mentioned, we saw really robust expansion of these CAR T-cells in the bloodstream of all treated subjects. At day 14, we saw robust expansion into the millions of CAR T-cells that freely got into the central nervous system. We saw them in the CSF of all patients who were infused. That means that those CAR-T molecules can be inside the central nervous system where other B-cell therapies, such as the large monoclonal antibodies, can’t get into so much. And then we saw clearance of the CAR T-cells typically by day 28. So one of the central questions is, if you give CAR T-cells to an MS patient, do they expand? Do they get into the bloodstream? Do they get into the CSF? And the answer, I’m happy to say, in our experience was strongly yes, we absolutely saw that.
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