ECTRIMS 2025 | The safety and feasibility of CAR-T in MS: findings from a Phase I trial

What we designed was a Phase I study where our primary outcome primarily was to look at feasibility and to look at safety first. We’re very excited about these results. It’s very important. You know, I would share with my colleagues, the numbers that we’re looking at are small. We’ve enrolled six subjects in the study that I’m going to be citing today although with plans to enroll a large number more going forward. To the first question is this feasible the answer is yes. In every case, in every subject that we enrolled, we were able to successfully obtain their T-cells by apheresis, we were able to successfully transduce that cell line using a lentivirus vector so that the patient’s own T-cells expressed a single chain variable fragment on the surface of the T-cell that recognize the CD19 glycoprotein. We enjoyed significant expansion so that we were able to infuse patients either with a one-time dose of either 33 million or 100 million cells. And the reason that we used those two different doses is that in working with our FDA here in the US, they insisted on a low and slow approach or what’s called a 3×3 design. In essence, they said try to minimize side effects and potential risks to your consenting subjects. Start with a low dose, in this case 33 million cells. Watch that one subject extremely closely to make sure they’re tolerating things well and there aren’t serious adverse events, and if we see evidence of safety you can proceed slowly. So we ended up in our cohort of six subjects to date, as of 2025, with three subjects treated with 33 million cells as a one-time infusion and three treated with 100 million cells as a one-time infusion. Our protocol was such that we had patients admitted and watched vigorously well in the hospital checked multiple times for any potential side effects for any serious adverse events of any kind. And our experience has been the infusions were very well tolerated. There was some mild nausea associated with bendamustine, but not more than that. And once the infusions were given, the patients frankly were kind of bored in the hospital because there was nothing more to do. They’d received their therapy. And for the first 10 days after treatment, none of them really experienced any significant side effects to speak of. Then on day 10, and this is true for every subject treated, what we observed was an abrupt onset of fever and it came on quickly. And we know that the fever was associated with the expansion of the T-cells that we infused. So those T-cells once they’re infused, they function like T-cells. They go into the body and they go into deep tissue, including the central nervous system and they look for targets. They’re trained to look for CD19, meaning B-cells. And if they recognize that target, the immune system is adjusted so that those cells will expand. And that’s what happened. The expansion itself of the cells is associated with an abrupt onset of fever. We only saw one case of all our treated subjects that would qualify for ICANS, and that was what’s listed as grade two, which is mild. The ICANS is thought to be associated with pro-inflammatory cytokines that are released as the immune system activates, thinking that it’s getting ready for a fight against a foreign invader. And it’s been known we have the great benefit of the giants who have walked in the path in front of us including those in neuroiminooncology, hence we used a medication called tocilizumab, which blocks IL6 and the patient felt better immediately, but otherwise all cases were treated with hydration and responded very well. They had fever for two to three days and then they returned to baseline, including their baseline neurologic function and their baseline neurologic strength.

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