Cyclodextrin-Based Supramolecular Carrier for Cancer Proteinaceous Antigen

Protein-based vaccines are gaining attention as a promising platform for vaccines because they are highly safe and induce humoral and cellular immunity. However, antigenic proteins have the disadvantages of low cell membrane permeability and easy degradability by endo/lysosomes. Therefore, the development of carriers that can overcome these challenges is essential. We recently developed a supramolecular carrier for the intracellular delivery of genome-editing molecules using cyclodextrin-based aminated polyrotaxanes (amino-PRX). The amino-PRX deformed its structure in response to the complicated shape and charge distribution of the genome-editing molecule, forming a complex with high efficiency. Moreover, by optimizing its structure, a second-generation amino-PRX (2G) possessing endosomal escape ability was constructed. Considering 2G deformability, it is applicable to antigenic proteins and could be an excellent antigen carrier. Therefore, here, we aimed to evaluate the utility of 2G as a protein-based cancer vaccine carrier. The results showed that 2G formed complexes with antigenic proteins efficiently. In addition, the 2G/antigenic protein complex activated immune cells with high efficiency and exhibited excellent antitumor effects. These results suggest that 2G is a promising protein-based cancer vaccine carrier.