OS11.4.A Intrathecal delivery of dendritic cell vaccine eradicates tumor growth and protects against leptomeningeal disease re-inoculation in immunocompetent HER2+ and triple negative breast cancer leptomeningeal disease xenograft models

Abstract Background Leptomeningeal disease (LMD) occurs in ~5% of patients with breast cancer (BC) and has a median survival 2-4 months. We found loss the anti-HER2 anti-HER3 CD4 Th1 immune responses BC patients. In pre-clinical clinical trials administration class II HER2 peptide-pulsed dendritic cell vaccine (HER2-DCV) partially restores pathologic complete HER2+ Here, we examined intrathecal (IT) delivery HER2/HER3-DCV BC-LMD immunocompetent animal models. Material Methods Luciferase-labeled TUBO BCs were injected into cisterna magna BALB/c mice to produce LMD. used our Murine Ommaya (mimics an reservoir clinically patients) for IT DCVs cerebral spinal fluid (CSF). Results randomized following groups: 1) HER2-DCV 2) HER3-DCV 3) IT. The untreated (control) group was 15 days. All groups given DCV prolonged (p<0.001). Interestingly, HER2-/HER3-DCV able rescue (71% 28% triple negative cancer-LMD) showed tumor regression. Some surviving subsequent rechallenge. CSF, evidence CD4+ CD8+ T-cells infiltration, robust IFN-gamma IL18 response upon treatment. Conclusion Our preclinical data supported trial (submitted)