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

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 mu g) 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 mu g) vaccine formulation significantly enhanced cellular and humoral immunity. The antitumor assays demonstrate that OVA/CaCO3/PLY (5 mu g) 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 mu g) offers a promising platform for the construction of efficient tumor vaccines.