{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Huff AL"],"funding":["Cancer Research UK","Mayo Foundation for Medical Education and Research","European Research Council","NIAID NIH HHS","University of Minnesota","Mayo Clinic","NCI NIH HHS","National Institutes of Health","NIGMS NIH HHS"],"pagination":["2540-2552"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7705043"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["28(12)"],"pubmed_abstract":["Enhancing the immunogenicity of tumor-associated antigens would represent a major advance for anti-tumor vaccination strategies. Here, we investigated structure-directed antigen destabilization as a strategy to improve the degradation, immunogenic epitope presentation, and T cell activation against a vesicular stomatitis virus (VSV)-encoded tumor antigen. We used the crystal structure of the model antigen ovalbumin to identify charge-disrupting amino acid mutations that were predicted to decrease the stability of the protein. One mutation, OVA-C12R, significantly reduced the half-life of the protein and was preferentially degraded in a 26-S proteasomal-dependent manner. The destabilized ovalbumin protein exhibited enhanced presentation of the major histocompatibility complex (MHC) class I "],"journal":["Molecular therapy : the journal of the American Society of Gene Therapy"],"pubmed_title":["Vesicular Stomatitis Virus Encoding a Destabilized Tumor Antigen Improves Activation of Anti-tumor T Cell Responses."],"pmcid":["PMC7705043"],"funding_grant_id":["P50 CA108961","R01CA108961","T32 AI132165","R01CA175386","P41 GM103311","R01 CA175386","P41-GM103311"],"pubmed_authors":["Kottke T","Evgin L","Tonne J","Wongthida P","Ramirez-Alvarado M","Shim KG","Vile R","Thompson J","Driscoll CB","Schuelke M","Huff AL","Mer G"],"additional_accession":[]},"is_claimable":false,"name":"Vesicular Stomatitis Virus Encoding a Destabilized Tumor Antigen Improves Activation of Anti-tumor T Cell Responses.","description":"Enhancing the immunogenicity of tumor-associated antigens would represent a major advance for anti-tumor vaccination strategies. Here, we investigated structure-directed antigen destabilization as a strategy to improve the degradation, immunogenic epitope presentation, and T cell activation against a vesicular stomatitis virus (VSV)-encoded tumor antigen. We used the crystal structure of the model antigen ovalbumin to identify charge-disrupting amino acid mutations that were predicted to decrease the stability of the protein. One mutation, OVA-C12R, significantly reduced the half-life of the protein and was preferentially degraded in a 26-S proteasomal-dependent manner. The destabilized ovalbumin protein exhibited enhanced presentation of the major histocompatibility complex (MHC) class I ","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Dec","modification":"2026-05-07T20:13:09.23Z","creation":"2022-02-11T13:29:42.069Z"},"accession":"S-EPMC7705043","cross_references":{"pubmed":["32877695"],"doi":["10.1016/j.ymthe.2020.08.013"]}}