Cross-presentation-based nanovaccine for cancer immunotherapy

Cross-presentation is an important mechanism by which dendritic cells (DCs) present exogenous antigens on major histocompatibility complex class I (MHC class I) molecules, and activate CD8+ T-cells that are crucial for the elimination of tumors. The induction of antitumor activity by targeting C-type lectin receptors (CLRs) such as DC-SIGN on DCs has become an interesting approach for cancer immunotherapy. Glycans are gaining importance in targeting of CLRs on antigen-presenting cells (APCs) in recent years due to their lower toxicity and immunogenicity. Targeting of DC-specific CLR such as DC-SIGN with glycan-modified cancer antigen facilitates not only its internalization but also favors antigen cross-presentation and stimulates tumor-specific CD4+ and CD8+ T-cell responses. Indeed, targeting of CLRs using specific glycan-coated nanocarriers entrapping cancer antigens also routs antigens to the cross-presentation pathway and induces a robust CD8+ T-cell response. Therefore, cross-presentation-based nanovaccine development could be a potential therapeutic approach for cancer since the existing cancer treatments such as chemotherapy and radiotherapy are not effective at the metastatic stage. The present chapter entails an overview of cross-presentation and its implication in cancer immunotherapy, glycans for effective targeting of CLRs for enhancing cross-presentation to improve T-cell response against tumor cells, and the use of glycan-coated nanocarriers for effective antigen delivery to APCs. Further, recent achievements in pH-responsive glycan-modified nanocarriers to induce cross-presentation via the endosomal escape of antigen have been summarized. The potential of plant lectins in the preparation of targeted nanovaccine for cancer immunotherapy has also been highlighted.