title: Insertion of exogenous epitopes in the E3-19K of oncolytic adenoviruses to enhance TAP-independent presentation and immunogenicity.
abstract: 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.
authors.affiliation: Translational Research Laboratory, IDIBELL-Institut Català d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Rodríguez-García
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratories, Uppsala University, Uppsala, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Svensson
authors.affiliation: Translational Research Laboratory, IDIBELL-Institut Català d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Gil-Hoyos
authors.affiliation: Translational Research Laboratory, IDIBELL-Institut Català d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: C A
authors.initials: CA
authors.lastname: Fajardo
authors.affiliation: Translational Research Laboratory, IDIBELL-Institut Català d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: L A
authors.initials: LA
authors.lastname: Rojas
authors.affiliation: Translational Research Laboratory, IDIBELL-Institut Català d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Arias-Badia
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratories, Uppsala University, Uppsala, Sweden.
authors.forename: A S I
authors.initials: AS
authors.lastname: Loskog
authors.affiliation: Translational Research Laboratory, IDIBELL-Institut Català d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Alemany
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D017503:Adenovirus E3 Proteins / Q000235:genetics*; D000260:Adenoviruses, Human / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation; D045744:Cell Line, Tumor; D000939:Epitopes / Q000235:genetics*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008810:Mice, Inbred C57BL; D016254:Mutagenesis, Insertional; D009369:Neoplasms / Q000628:therapy*; D050504:Oncolytic Viruses / Q000235:genetics*
chemical_list: D018528:ATP-Binding Cassette Transporters; D017503:Adenovirus E3 Proteins; C084390:E3 glycoprotein 19k, Adenovirus type 7; D000939:Epitopes; C477327:transporter associated with antigen processing (TAP)