Vaccination with an adenoviral vector encoding the tumor antigen directly linked to invariant chain induces potent CD4+ T‐cell‐independent CD8+ T‐cell‐mediated tumor control

Antigen‐specific immunotherapy is an attractive strategy for cancer control. In the context of antiviral vaccines, adenoviral vectors have emerged as a favorable means for immunization. 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‐associated neoantigen. Prophylactic vaccination of C57BL/6 mice with a replication‐deficient human adenovirus 5 vector encoding GP linked to Ii (Ad‐Ii‐GP) resulted in complete protection against GP33‐expressing B16.F10 tumors. Therapeutic vaccination with Ad‐Ii‐GP delayed tumor growth by more than 2 wk compared with sham vaccination. Notably, therapeutic vaccination with the linked vaccine was significantly better than vaccination with adenovirus expressing GP alone (Ad‐GP), or GP and Ii unlinked (Ad‐GP+Ii). Ad‐Ii‐GP‐ induced tumor control depended on an improved generation of the tumor‐associated neoantigen‐specific CD8⁺ T‐cell response and was independent of CD4⁺ T cells. IFN‐γ was shown to be a key player during the tumor degradation. Finally, Ad‐Ii‐GP but not Ad‐GP vaccination can break the immunological non‐reactivity in GP transgenic mice indicating that our vaccine strategy will prove efficient also against endogenous tumor antigens.