EXTH-01. INTRATHECAL DELIVERY OF DENDRITIC CELL VACCINE ERADICATES TUMOR GROWTH AND PROTECTS AGAINST LEPTOMENINGEAL DISEASE RE-INOCULATION IN HER2+ AND TRIPLE NEGATIVE BREAST CANCER LMD XENOGRAFT MODELS. (14th November 2022)

• Record Type: Journal Article
• Authors: Law, Vincent; Kodomudi, Krithika; Snyder, Colin; Forsyth, Peter; Czerniecki, Brian
• Is Part Of: Neuro-oncology. Volume 24(2022)Supplement 7
• Page Start: vii208
• Page End: vii208
• Publication Date: 2022-11-14
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noac209.800
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: BACKGROUND: Leptomeningeal disease (LMD) occurs in approximately 5% of patients with breast cancer 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 breast cancer 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+ breast cancer patients. Here, we examined the intrathecal (IT) delivery of HER2/HER3-DCV in breast cancer-associated LMD immunocompetent animal models. METHODS: Luciferase-labeled HER2+ TUBO breast cancer cells were injected into the cisterna magna of BALB/c mice to produce LMD. We used our Murine Ommaya (mimics an Ommaya reservoir in patients) for the IT administration of DCVs into the CSF. RESULTS AND DISCUSSION: breast cancer-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+ breast cancer-LMD and 28% in triple negative breast cancer-LMD) and showed complete tumor regression. Some surviving mice were immune to subsequent tumor rechallenge. In mice CSF, we found evidence of CD4+ and CD8+ T-cells infiltration, and robust IFN-g and IL18 response upon DCV treatment. CONCLUSIONS: Our preclinical data supported a clinical trial (submitted) of the IT delivery of DCV in breast cancer patients with LMD.