Peptide-based assemblies as immune checkpoint inhibitor delivery systems for enhanced immunotherapy

Abstract In recent years, with the continuous development of cancer immunotherapy, the strategy of human beings against cancer has undergone tremendous changes. Among them, immune checkpoint inhibitors based on the immune "brake" mechanism, as an indispensable part of immunotherapy, have brought new dawn to cancer treatment. Humans have developed a variety of monoclonal antibodies against CTLA-4 and PD-1/PD-L1, which have shown significant therapeutic effects on various cancers, especially melanoma. Several monoclonal antibodies have been approved for clinical treatment and obtained exciting clinical benefits. However, immune checkpoint therapy is still plagued by two shortcomings: low response rate and high side effects. Polypeptides have broad application prospects in the field of drug delivery due to their low immunogenicity, low toxicity and versatility. Peptide-based assemblies with specificity and safety can be used for targeted delivery of immune checkpoint inhibitors. Strategies such as PEG modification and “reassembly in vivo” can effectively increase the response rate of immune checkpoint inhibitors and reduce side effects. This review introduces multiple types of immune checkpoints and peptide-based assemblies for immune checkpoint inhibitor delivery, and the roles of peptides in these assembles are described in detail. The synergistic effect of immune checkpoint blockade and other therapies to enhance antitumor immunotherapy is emphasized.