Abstract BACKGROUND Leptomeningeal disease (LMD) is a devastating complication of breast cancer (BC) where it occurs in approximately 5% of patients and has a poor prognosis. The CSF of patients with LMD have an innate, but not adaptive, immune cellular profile. We found in murine LMD models IT cDC1s were safe, induced a Th1 response, cured most HER2+ LMD, and prevented LMD recurrence. This provoked a Th1 response, was CD4+ CD8+ T cell and B cell dependent. Mechanistic studies are in progress. Therefore, we hypothesized in BC LMD patients that a RP2D would be identified, and the CSF would be remodeled to have a Th1 adaptive immunological profile identified by transcriptomic analysis. MATERIAL AND METHODS This is a phase I single-arm, non-randomized dose escalation multicenter study (NCT05809752) to establish 1) the safety of IT cDC1s, and 2) associations between clinical outcomes the Th2-related IL-4 was not elevated. Transcriptomic analyses of CSF showed a remodeled environment with marked increase in CD4+ T, CD8+ T and B cells with a reduction of tumor cells. Antibodies to HER2 or HER3 developed in four of five (80%) patients. CONCLUSION Our results suggest that this approach activates CD4+ Th1 adaptive immune responses that drives adaptive antitumor activity which is otherwise lacking in LMD(NCT05809752). Mechanistic studies are in progress.
Forsyth et al. (Wed,) studied this question.