Dendritic cell vaccine for the effective immunotherapy of breast cancer
ABSTRACT
Cancer vaccine is widely considered as a powerful tool in immunotherapy. In particular, the effective antigen processing and presentation natures of dendritic cell (DC) have made it a promising target for the development of therapeutic vaccine for cancer treatment. Here in our study, a versatile cancer cell membrane (CCM) coated calcium carbonate (CC) nanoparticles (MC) that capable of generating in situ tumor-associated antigens (TAAs) for DC vaccination is developed. Low-dose doxorubicin hydrochloride (Dox) could be encapsulated in the CC core of MC to trigger immunogenic cell death (ICD) while chlorins e6 (Ce6), a commonly adopted photosensitizer, was loaded in the CCM of MC for effective photodynamic therapy (PDT) through the generation of reactive oxygen species (ROS) to finally construct the vaccine (MC/Dox/Ce6). Most importantly, our in-depth study revealed the treatment of MC/Dox/Ce6 was able to elicit TAAs population and DC recruitment, triggering the following immune response cascade. In particular, the recruited DC cells could be stimulated in situ for effective vaccinations. Both in vitro and in vivo experiments suggested the capability of this all-in-one DDS to enhance DCs maturation to finally result in effective inhibition of both primary and distant growth of breast cancer upon single administration of low dose Dox and Ce6.