Using Intrathecal Dendritic Cells for Leptomeningeal Disease From Breast Cancer

At the 2026 SNO ASCO CNS Metastases Conference, Peter Forsyth, MD, discussed a single-arm, dose-escalation, phase 1 trial (NCT05809752) evaluating the intrathecal delivery of conventional type 1 dendritic cells (cDC1s) in patients with HER2-positive or triple-negative breast cancer and leptomeningeal disease. As of data reported in his abstract from March 26, 2026, among 14 patients, grade 3 headache occurred in 57%, and dose-limiting toxicities (DLTs) occurred in 14% of patients treated at the highest dose level (5 × 10⁷ cells). This prompted de-escalation to 1 × 10⁷ cells, at which no DLTs had been observed to date. Cytokine and transcriptomic analyses in a subset of patients showed increased Th1-associated cytokines without a corresponding rise in IL-4, and single-cell RNA sequencing demonstrated expansion of CD4-positive, CD8-positive, γδ T cells, and B cells.