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Therefore, we chose a strategy combining use of these vectors with another successful approach, namely linkage of the vaccine antigen to invariant chain (Ii). To evaluate this strategy we used a mouse model, in which an immunodominant epitope (GP33) of the LCMV glycoprotein (GP) represents the tumor\u2010associated neoantigen. Prophylactic vaccination of C57BL\/6 mice with a replication\u2010deficient human adenovirus 5 vector encoding GP linked to Ii (Ad\u2010Ii\u2010GP) resulted in complete protection against GP33\u2010expressing B16.F10 tumors. Therapeutic vaccination with Ad\u2010Ii\u2010GP delayed tumor growth by more than 2\u2009wk compared with sham vaccination. Notably, therapeutic vaccination with the linked vaccine was significantly better than vaccination with adenovirus expressing GP alone (Ad\u2010GP), or GP and Ii unlinked (Ad\u2010GP+Ii). Ad\u2010Ii\u2010GP\u2010 induced tumor control depended on an improved generation of the tumor\u2010associated neoantigen\u2010specific CD8<jats:sup>+<\/jats:sup> T\u2010cell response and was independent of CD4<jats:sup>+<\/jats:sup> T cells. IFN\u2010\u03b3 was shown to be a key player during the tumor degradation. Finally, Ad\u2010Ii\u2010GP but not Ad\u2010GP vaccination can break the immunological non\u2010reactivity in GP transgenic mice indicating that our vaccine strategy will prove efficient also against endogenous tumor antigens.<\/jats:p>","DOI":"10.1002\/eji.200939543","type":"journal-article","created":{"date-parts":[[2009,7,27]],"date-time":"2009-07-27T11:51:34Z","timestamp":1248695494000},"page":"2725-2736","source":"Crossref","is-referenced-by-count":42,"title":["Vaccination with an adenoviral vector encoding the tumor antigen directly linked to invariant chain induces potent CD4<sup>+<\/sup> T\u2010cell\u2010independent CD8<sup>+<\/sup> T\u2010cell\u2010mediated tumor control"],"prefix":"10.1002","volume":"39","author":[{"given":"Maria R.","family":"Sorensen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J.","family":"Holst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanspeter","family":"Pircher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan P.","family":"Christensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allan R.","family":"Thomsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,10,2]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2478(00)00244-3"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2006.00442.x"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-2517"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061890"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200526175"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.100201.131730"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.14.1.207"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2006.05.005"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.11.5966-5972.2004"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.5.3339"},{"key":"e_1_2_6_12_2","unstructured":"Holst P. 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