Cellular hitchhiking is an emerging strategy for the in vivo control of adoptively transferred immune cells. Hitchhiking approaches are primarily mediated by adhesion of nano and microparticles to the cell membrane, which conveys an ability to modulate transferred cells via local drug delivery. Although T cell therapies employing this strategy have progressed into the clinic, phagocytic cells including dendritic cells (DCs) are much more challenging to engineer. DC vaccines hold great potential for a spectrum of diseases, and the combination drug delivery is an attractive strategy to manipulate their function and overcome in vivo plasticity. However, DCs are not compatible with current hitchhiking approaches due to their broad phagocytic capacity. In this work, we developed and validated META (membrane engineering using tannic acid) to enable DC cellular hitchhiking for the first time. META employs the polyphenol tannic acid (TA) to facilitate supramolecular assembly of protein drug cargoes on the cell membrane, enabling the creation of cell surface-bound formulations for local drug delivery to carrier DCs. We optimized META formulations to incorporate and release protein cargoes with varying physical properties alone and in combination and to preserve DC viability and critical functions such as migration. We further show that META loaded with either a pro- or anti-inflammatory cargo can influence the carrier cell phenotype, thus demonstrating the flexibility of the approach for applications from cancer to autoimmune disease. Overall, this approach illustrates a new platform for the local control of phagocytic immune cells as a next step to advance DC therapies in the clinic.
Keywords: cell therapy; dendritic cells; immunotherapy; phenolic network; vaccines.