Nanovaccine designed for splenic delivery augments immune responses for tumor therapy

Spleen is an ideal secondary lymphoid organ for initiating and amplifying tumor-specific immunity; however, suboptimal antigen delivery and immune activation cause immune tolerance, limited tumor therapeutic efficacy and undesired side effects. Herein, we designed a spleen targeted nanovaccine that can carry tumor antigens and microRNA-155 (miR155) to spleen, achieving sufficient and persistent immune responses. To encapsulate miR155, we synthesized a glutathione (GSH)-responsive cationic polymer (PADDAC) that spontaneously self-assembled with miR155 to form nanocomplexes. Afterwards, the nanocomplexes were infused with tumor cell and erythrocyte membranes, granting them the ability to carry tumor associated antigens (TAAs) and target splenic antigen-presenting cells, respectively. We found that the nanovaccine demonstrated spleen-selective accumulation and efficient cytotoxic T lymphocyte activation with protective immune memory. This significantly inhibited the growth of the primary tumor and hindered the development of pulmonary metastasis in a tumor harboring mouse model. Moreover, we generated a personalized nanovaccine, which reduced local tumor recurrence post-surgery. This study highlighted the potential of splenic targeting nanovaccine for tumor preventative and therapeutic applications.