Abstract
Abstract Human epidermal growth factor receptor 2 (HER2)+ cancers are aggressive, have poor prognoses, high rate of metastasis and relapse. Immunotherapy (e.g. trastuzumab) has shown improvement in outcome for HER2+ patients. Development of drug resistance and short half-lives limiting the duration of the therapy, are barriers in the development of effective therapeutic strategies. Furthermore, while passive immunotherapy provides treatment, it does not reduce the risk of recurrence of the disease. Therefore, we propose a HER2 vaccine to mount an active HER2-specific immune response, with long lasting immunological memory to overcome the limitations of passive immunotherapy and prevent tumor progression, metastasis, and relapse. We hypothesize that integration of HER2 epitopes on the plant-produced vaccination platform potato virus X (PVX) will overcome immunological tolerance against HER2. We have shown that PVX naturally targets dendritic and B-cells stimulating Th1 biased immunity, important for successful tumor prevention. The carrier acts as an adjuvant, improves stability of epitopes, and increases circulation time, therefore ensuring a sustained stimulus post vaccination and production of HER2-specific antibodies that could act against HER2+ tumors via a variety of effector mechanisms. Immunizations of FBV/N mice resulted in the production of HER2-specific antibodies, as shown by ELISA and confocal microscopy using HER2+ human cancer cell lines. Vaccination studies using animals pre-disposed to HER2+ cancer are currently ongoing. Our long-term goal is to produce the vaccine through molecular farming in edible plant tissue and make it available globally, especially in underdeveloped countries where repeated administration of costly immunotherapies is not affordable or unavailable. Citation Format: Sourabh Shukla, Nicole F. Steinmetz. Molecular farming and molecular engineering of cancer vaccines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2887. doi:10.1158/1538-7445.AM2014-2887
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