دورية أكاديمية
أعرض في EDS

Vesicular Stomatitis Virus Encoding a Destabilized Tumor Antigen Improves Activation of Anti-tumor T Cell Responses.

التفاصيل البيبلوغرافية
العنوان: Vesicular Stomatitis Virus Encoding a Destabilized Tumor Antigen Improves Activation of Anti-tumor T Cell Responses.
المؤلفون: Huff AL; Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA; Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN 55905, USA., Evgin L; Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA., Thompson J; Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA., Kottke T; Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA., Driscoll CB; Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA; Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN 55905, USA., Tonne J; Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA., Wongthida P; Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA., Schuelke M; Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA., Shim KG; Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA., Mer G; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA., Ramirez-Alvarado M; Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA., Vile R; Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA; Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA; Leeds Institute of Cancer and Pathology, Faculty of Medicine and Health, University of Leeds, St James's University Hospital, Beckett Street, Leeds, West Yorkshire LS9 7TF, UK. Electronic address: vile.richard@mayo.edu.
المصدر: Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2020 Dec 02; Vol. 28 (12), pp. 2540-2552. Date of Electronic Publication: 2020 Aug 25.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 100890581 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-0024 (Electronic) Linking ISSN: 15250016 NLM ISO Abbreviation: Mol Ther Subsets: MEDLINE
أسماء مطبوعة: Publication: 2017- : Cambridge, MA : Cell Press
Original Publication: San Diego, CA : Academic Press, 2000-
مواضيع طبية MeSH: Immunity* , Lymphocyte Activation*, Antigens, Neoplasm/*genetics , CD8-Positive T-Lymphocytes/*immunology , Genetic Vectors/*immunology , Ovalbumin/*genetics , Vesiculovirus/*genetics, Animals ; Antigen Presentation ; Antigens, Neoplasm/chemistry ; Cancer Vaccines/immunology ; Cell Line, Tumor ; Dendritic Cells/immunology ; Epitopes/immunology ; Female ; HEK293 Cells ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Oncolytic Virotherapy/methods ; Ovalbumin/chemistry ; Protein Stability
مستخلص: 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 immunogenic epitope, SIINFEKL, on the surface of B16F10 cells or murine bone marrow-derived dendritic cells (BMDCs) in vitro. Enhanced presentation correlated with better recognition by cognate CD8 OT-I T cells as measured by activation, proliferation, and effector cytokine production. Finally, VSV encoding the degradation-prone antigen was better able to prime an antigen ovalbumin-specific CD8 T cell response in vivo without altering the anti-viral CD8 T cell response. Our studies highlight that not only is the choice of antigen in cancer vaccines of importance, but that emphasis should be placed on modifying antigen quality to ensure optimal priming of anti-tumor responses.
(Copyright © 2020. Published by Elsevier Inc.)
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معلومات مُعتمدة: T32 AI132165 United States AI NIAID NIH HHS; P50 CA108961 United States CA NCI NIH HHS; P41 GM103311 United States GM NIGMS NIH HHS; R01 CA175386 United States CA NCI NIH HHS; United Kingdom CRUK_ Cancer Research UK
فهرسة مساهمة: Keywords: anti-tumor T cell response, oncolytic virus, viral immunotherapy; antigen presentation; protein degradation; vesicular stomatitis virus
المشرفين على المادة: 0 (Antigens, Neoplasm)
0 (Cancer Vaccines)
0 (Epitopes)
9006-59-1 (Ovalbumin)
تواريخ الأحداث: Date Created: 20200903 Date Completed: 20210914 Latest Revision: 20211203
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC7705043
DOI: 10.1016/j.ymthe.2020.08.013
PMID: 32877695
قاعدة البيانات: MEDLINE
الوصف
تدمد:1525-0024
DOI:10.1016/j.ymthe.2020.08.013