Abstract B32: Preclinical testing of three immune adjuvants in vaccination therapy for invasive canine meningioma.

Abstract

Abstract Malignant and atypical meningiomas are resistant to standard therapies, but therapeutic vaccines have not been tested preclinically or clinically. Pet dogs with naturally occurring meningioma are an underutilized model for aggressive human meningioma and an outstanding opportunity for assessing experimental therapeutic approaches. We treated 11 meningioma-bearing dogs with surgery and vaccine immunotherapy consisting of autologous tumor cell lysate combined with CpG or imiquimod. Interferon gamma-elaborating T cells were detected in the peripheral blood of two of cases, but vaccine-induced tumor-reactive antibody responses were found in the sera of all dogs. Systemic antibody responses were polyclonal, recognizing intracellular and cell surface antigens, and heat shock protein 60 was identified as one common antigen. Tumor-reactive antibodies bound allogeneic canine and human meningiomas, demonstrating common antigens across breed and species. Histological analysis revealed robust infiltration of antibody-secreting plasma cells into the brain around the tumor in treated compared to pre-treatment samples. Tumor-reactive antibodies were capable of inducing antibody dependent cell-mediated cytotoxicity to autologous and allogeneic tumor cells. Moreover, median survival for lysate/CpG and lysate/imiquimod vaccination was 646 days versus 222 days in historic surgery controls (p<0.05). Compared to CpG, a novel imidazoquinoline with TLR7/8 and inflammasome activity, compound 528, was equally potent at activating canine PBMCs. A prospective randomized two-arm trial was recently launched, using lysate—compound 528 vaccines, versus surgery controls. Mean follow-up is 139 days at the time of writing, and recruitment is ongoing. These data demonstrate the feasibility and immunologic efficacy of vaccine immunotherapy for treating a large animal model of human meningioma and warrant further development towards human trials. Citation Format: Brian M. Andersen, G Elizabeth Pluhar, Charles E. Seiler, Zhengming Xiong, Michelle R. Goulart, Matthew Gerry O'Sullivan, Matthew A. Hunt, Charles E. Schiaffo, David M. Ferguson, John R. Ohlfest. Preclinical testing of three immune adjuvants in vaccination therapy for invasive canine meningioma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B32.