In Situ Modification of the Tumor Cell Surface with Immunomodulating Nanoparticles for Effective Suppression of Tumor Growth in Mice

Current cancer immunotherapies including chimeric antigen receptor (CAR)‐based therapies and checkpoint immune inhibitors have demonstrated significant clinical success, but always suffer from immunotoxicity and autoimmune disease. Recently, nanomaterial‐based immunotherapies are developed to precisely control in vivo immune activation in tumor tissues for reducing immune‐related adverse events. However, little consideration has been put on the spatial modulation of interactions between immune cells and cancer cells to optimize the efficacy of cancer immunotherapies. Herein, a rational design of immunomodulating nanoparticles is demonstrated that can in situ modify the tumor cell surface with natural killer cell (NK cell)‐activating signals to achieve in situ activation of tumor‐infiltrating NK cells, as well as direction of their antitumor immunity toward tumor cells. Using these immunomodulating nanoparticles, the remarkable inhibition of tumor growth is observed in mice without noticeable side effects. This study provides an accurate immunomodulation strategy that achieves safe and effective antitumor immunity through in situ NK cell activation in tumors. Further development by constructing interactions with various immune cells can potentially make this nanotechnology become a general platform for the design of advanced immunotherapies for cancer treatments. An immunomodulating nanoparticle is developed to in situ modify tumor cell surfaces with immune‐activating ligands. Such modification achieves the activation of tumor‐infiltrating natural killer cells, leading to an enhanced antitumor performance without noticeable side effects. This study provides an accurate immunomodulation strategy that achieves safe and effective antitumor immunity through in situ natural killer cell activation in tumors.