Localized PD-1 CAR T therapy reprograms neuroinflammation.

Localized PD-1 CAR T therapy effectively reprograms neuroinflammation, reducing CNS inflammation and improving outcomes in murine models of multiple sclerosis.

• Why it matters: Current B cell-depleting treatments for MS can lead to relapses, highlighting the need for more precise, targeted therapies that address specific immune mechanisms within the CNS.
• What they did: Using single-cell RNA sequencing of CSF, brain, and blood from patients and controls, the study identified a disease-enriched subset of PD-1+ T follicular helper-like cells and developed PD-1 CAR T cells to target them, releasing IL-10 locally.
• The result: This approach selectively depletes pathogenic T cells, attenuates neuroinflammation, reprograms the immune environment, and enhances clinical outcomes, offering a promising new strategy for MS treatment.