Abstract Most cancer cells carry mutations unique to the patient’s individual tumor and shared biochemical signatures that are not present in healthy cells. Agenus has three vaccine platforms designed to treat cancers based on the unique needs of a given patient. Our vaccine platforms are designed to educate the patient’s immune system to recognize tumor-specific aberrations, or neo-antigens, and mount an anti-tumor immune response. Agenus’ Prophage™ vaccine platform is an individualized vaccine made from the patient’s own tumor tissue. Heat shock proteins (gp-96) that naturally chaperone and bind tumor-derived peptides are extracted from the patient’s tumor and constitute the vaccine. Some of these peptides are neo-antigens. Agenus has completed Phase 2 clinical trials with Prophage™ vaccine in newly diagnosed glioblastoma (ndGBM), and has previously reported that there was improved progression-free and overall survival with Prophage™ vaccine compared to standard of care. Agenus’ AutoSynVax™ vaccines are uniquely designed and manufactured for each patient based on NGS profiling of the patient’s tumor from a biopsy. Leveraging the Agenus Immunogenic Mutation (AIM™) workflow, we are able to generate a synthesis-ready blueprint for an optimal immunogenic and personalized neo-antigen vaccine. The AIM™ platform provides a robust and efficient approach to computational vaccinology designed to deliver a set of likely immunogenic peptides, agnostic to vaccine format, followed by generation of a format-specific blueprint ready for vaccine synthesis and manufacture. The synthesized neo-epitopes are complexed to recombinant heat shock protein 70 (HSC70) and are administered along with our QS-21 Stimulon® adjuvant. HSC70 is known to transport epitopes and play a role in displaying them to T cells. While the first two of Agenus’ vaccine platforms are highly individualized, our PhosphoSynVax™ vaccine is an off-the-shelf vaccine format targeting a novel class of tumor neo-antigens arising from post translational modifications (PTMs). Due to dysregulated cell signaling pathways in cancer, self-peptides can be aberrantly phosphorylated, a number of which are subsequently presented on HLA molecules. Using mass-spectrometry, we have identified a library of over a thousand HLA phospholigands. Many of these are tumor specific and found in multiple patients across multiple indications, enabling pre-manufacture of PhosphoSynVax™ vaccines for ready use. Upon testing the HSP plus synthetic peptide vaccine format in murine models, we have demonstrated effective tumor control in a therapeutic setting and also effective immune memory in a long-term prophylactic setting. Given Agenus’ diverse portfolio we have the opportunity to combine our immune education strategies with immunomodulatory antibodies to increase therapeutic efficacy. Citation Format: Mohamed Uduman, Mithun Khattar, Bishnu Joshi, Antoine Tanne, Benjamin Morin, Armen Karapetyan, Elise Drouin, Sandra Craig, Paisley Myers, Erin Jeffery, Nicholas Wilson, Amy Yang, Victor H. Engelhard, Mark Cobbold, Donald F. Hunt, Dennis Underwood, Shiwen Lin, Mark Findeis, Jeffrey Raizer, John Goldberg, Jennifer S. Buell, Robert Stein, Daniel L. Levey, John Castle. Agenus’ next generation cancer vaccine platforms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4609. doi:10.1158/1538-7445.AM2017-4609