Multimode CaCO3/pneumolysin antigen delivery systems for inducing efficient cellular immunity for anti-tumor immunotherapy

Abstract

Along with the clinical success of tumor immunotherapy, development of tumor vaccines has attracted more and more attention, the key of which is to induce efficient tumor antigen-specific cellular immunity. This usually relies on using intelligent antigen delivery systems to realize the cytoplasmic delivery and cross-presentation of exogenous tumor antigens to CD8+ T cells. In this study, multi-functional vaccine adjuvant pneumolysin (PLY) and carrier calcium carbonate (CaCO3) nanoparticles are combined by physical absorption of PLY onto CaCO3 nanoparticles to construct multimode antigen delivery systems CaCO3/PLY to induce cellular immunity for tumor vaccines. Here, both CaCO3 nanoparticles and PLY were adopted to induce the lysosomal escape, cytoplasmic delivery and cross-presentation of exogenous antigens to enhance cellular immunity. Based on this, minimalist tumor vaccines were prepared in a one-pot method through physical adsorption of model antigen ovalbumin (OVA) and PLY onto CaCO3 nanoparticles, termed as OVA/CaCO3/PLY. The in vitro results showed that OVA/CaCO3/PLY (5 μg) vaccine formulation promoted antigen cross-presentation by inducing effective lysosome escape and cytoplasmic delivery of the antigen protein OVA. The in vivo immunization results show that OVA/CaCO3/PLY (5 μg) vaccine formulation significantly enhanced cellular and humoral immunity. The anti-tumor assays demonstrate that OVA/CaCO3/PLY (5 μg) vaccine formulation displayed significantly effective preventive and therapeutic anti-tumor efficacy. Collectively, both CaCO3 nanoparticles and an appropriate dose of PLY contributed to strong anti-tumor cellular immunity. The multimode antigen delivery system CaCO3/PLY (5 μg) offers a promising platform for the construction of efficient tumor vaccines.