Abstract

Abstract Vaccination is a widely‐accepted resort against the invasion or proliferation of bacteria, parasites, viruses, and even cancer, which accounts heavily on an active involvement of CD8 + T cells. As one of the pivotal strategies taken by dendritic cells (DCs) to promote the responsiveness of CD8 + T cells to exogenous antigens, cross presentation culminates in an elevated overall host defense against cancer or infection. However, the precise mechanisms regulating such a process remains elusive, and current attempts to fuel cross presentation usually fail to exert efficiency. Here, model antigen OVA‐loaded, endoplasmic reticulum (ER)‐targeting cationic liposome (OVA@lipoT) is developed and characterized with a booster effect on the activation and maturation of DCs. Moreover, OVA@lipoT pulsed DCs exhibit overwhelming superiority in triggering cytotoxic T lymphocyte response both in vivo and in vitro. Data reveal that lipoT alters the intracellular trafficking and presenting pathway of antigen, which promotes cross presentation and bears close relationship to the ER‐associated degradation (ERAD). These results may drop a hint about the interconnectivity between cross presentation and ER‐targeted antigen delivery, provide extra information to the understanding of ERAD‐mediated cross priming, and even shed new light on the design and optimization of vaccines against currently intractable cancers or virus‐infection.