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Insertion of exogenous epitopes in the E3-19K of oncolytic adenoviruses to enhance TAP-independent presentation and immunogenicity
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
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2015 (English)In: Gene Therapy, ISSN 0969-7128, E-ISSN 1476-5462, Vol. 22, no 7, 596-601 p.Article in journal (Refereed) Published
Abstract [en]

Oncolytic adenoviruses can promote immune responses against tumors by expressing and/or displaying tumor-associated antigens. However, the strong immunodominance of viral antigens mask responses against tumor epitopes. In addition, defects in major histocompatibility complex class I antigen presentation pathway such as the downregulation of the transporter-associated with antigen processing (TAP) are frequently associated with immune evasion of tumor cells. To promote the immunogenicity of exogenous epitopes in the context of an oncolytic adenovirus, we have taken advantage of the ER localization of the viral protein E3-19K. We have inserted tumor-associated epitopes after the N-terminal signal sequence for membrane insertion of this protein and flanked them with linkers cleavable by the protease furin to facilitate their TAP-independent presentation. This strategy allowed an enhanced presentation of the exogenous epitopes in TAP-deficient tumor cells in vitro and the generation of higher specific immune responses in vivo that were able to significantly control tumor growth.

Place, publisher, year, edition, pages
2015. Vol. 22, no 7, 596-601 p.
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:uu:diva-259104DOI: 10.1038/gt.2015.41ISI: 000357425300010PubMedID: 25994521OAI: oai:DiVA.org:uu-259104DiVA: diva2:843445
Available from: 2015-07-28 Created: 2015-07-27 Last updated: 2017-12-04Bibliographically approved

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Svensson, EmmaLoskog, Angelica

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Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

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