A Novel Antigen Delivery System for Cancer Immunotherapy Using Antigens Linked to Inactivated <i>Salmonella</i> Bacteria

Targeted delivery of antigens to antigen-presenting cells (APCs) seems to be an improved scheme in cancer immunotherapy. In this work, a new bacterial vaccine vector was designed by conjunction of antigen onto the surface of it through the linkage of heparin in aqueous solution. These bacterial particles were uniform in size with the diameter of ∼1 μ m and can be effectively internalized by dendritic cells (DCs). As a model antigen, Ovalbumin (OVA) was conjugated onto the surface of Salmonella bacterial through the chemical reaction of carboxy group in activated heparin and the amino group in OVA, forming Sal-OVA micro-particles. The drug loading efficiency is approximately 20%. Antigen delivery mediated by Salmonella improved the cellular uptake of antigens by DCs and the potency of Salmonella -modified micro-capsules to activate DCs was demonstrated by increased expression of maturation makers CD40 and CD86. Additionally, the functional relevance of the induced immune response was validated in murine E.G-7 tumors in vivo . Adoptive immunotherapy experiments indicated that serum and T lymphocytes in Sal-OVA immunized mice had anticancer effect on E.G-7 tumor, implying that both humoral immunity and cellular immunity induced by Sal-OVA may participate in the protective immunotherapy. These results highlight the potential of Sal-OVA microparticles for cancer immunotherapy.