Magnetic Metal Micelles for Enhanced Delivery of Self-Immolating CD8(+) T-Cell Epitopes for Cancer Immunotherapy

Cancer peptide vaccines face challenges for antigen delivery and presentation. In the present work, we develop a self-assembled magnetic micelle delivery system for CD8(+) T-cell epitopes that produces strong cellular immune responses. Hydro-phobically modified imiquimod R837 and Zn1.15Fe1.85O4 are coencapsulated in the core of Pluronic F127 block copolymer micelles. Magnetic Zn1.15Fe1.85O4 enables externally targeted delivery and enrichment of micelles in lymph nodes. Furthermore, metal ions are found to enhance vaccine immunogenicity. F127 micelles were chemically modified by a self-immolative linker so that antigens are rapidly and reversibly grafted on micelles in an aqueous solution. With the assistance of an external magnetic field, once the magnetic micelles are delivered to lymph nodes and taken up by immune cells, intracellular glutathione cleaves the disulfide bond and releases pristine short peptide antigen. Delivery to lymph nodes is tracked by magnetic resonance and fluorescence imaging. The use of this vaccine system eradicated tumors in a murine tumor model. Thus, integrating multiple functionalities in a single micellar delivery system, including responsive linkage, multiple immunostimulatory molecules, targeted delivery, and bimodal imaging, demonstrates the potential for theranostic approaches to develop a new generation of cancer vaccines.