Bsci-01 intrathecal delivery of dendritic cell vaccine eradicates tumor growth and protects against leptomeningeal disease (lmd) re-inoculation in immunocompetent her2+ and triple negative breast cancer (tnbc) lmd xenograft models

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