Laser-Activatable In Situ Vaccine Enhances Cancer-Immunity Cycle

The immune response in cancer reflects a series of carefully regulated events; however, current tumor immunotherapies typically address a single key aspect to enhance anti-tumor immunity. In the present study, a nanoplatform (Fe3O4@IR820@CpG)-based immunotherapy strategy that targets the multiple key steps in cancer-immunity cycle is developed: 1) promotes the release of tumor-derived proteins (TDPs), including tumor-associated antigens and pro-immunostimulatory factors), in addition to the direct killing effect, by photothermal (PTT) and photodynamic therapy (PDT); 2) captures the released TDPs and delivers them, together with CpG (a Toll-like receptor 9 agonist) to antigen-presenting cells (APCs) to promote antigen presentation and T cell activation; 3) enhances the tumor-killing ability of T cells by combining with anti-programmed death ligand 1 antibody (alpha-PD-L1), which collectively advances the outstanding of the anti-tumor effects on colorectal, liver and breast cancers. The broad-spectrum anti-tumor activity of Fe3O4@IR820@CpG with alpha-PD-L1 demonstrates that optimally manipulating anti-cancer immunity not singly but as a group provides promising clinical strategies. An in situ tumor vaccine is constructed to regulate the multiple events in the tumor immunity cycle: enhances antigen release by PTT and PDT; captures and delivers the released antigen, together with CpG, to APCs for antigen presentation; promotes T cell killing effect by combining with immune checkpoint inhibitor, thus significantly increasing the anti-tumor effectiveness on colorectal, liver and breast cancer.image