Tumor growth control using red blood cells as the antigen delivery system and poly(I:C)

The goal of most current vaccines in tumor immunology is to induce an efficient immune response against the tumor cells. The use of red blood cells (RBCs) for the delivery of tumor-associated antigen to antigen-presenting cells is an innovative approach for cancer immunotherapy. The induction of antigen-specific immune responses after administration of antigen-loaded RBCs has been demonstrated previously in mice. In this paper, we show the utility of this delivery system for cancer immunotherapy in 2 tumor mouse models, using the E.G7-OVA and the B16F10 tumor cells. The non-self-antigen, ovalbumin, loaded in RBCs and the self-tumor antigen, tyrosinase-related protein 2, loaded in RBCs were tested in the E.G7-OVA and the B16F10 tumor models, respectively. We showed that not only protein but also peptide could be efficiently entrapped in RBCs by a controlled lysis/resealing process. In both antigen models, the administration of a small quantity of antigen loaded in RBCs combined with polyinosinic-polycytidylic acid induced an antigen-specific T-cell response and the control of tumor growth in mice, whereas the injection of the same quantity of free antigen did not. The intensity of the T-cell response was dependent on the concentrations of antigen entrapped and the treatment performed on the RBC membrane (antibody coating and heat treatment) to improve antigen delivery. In summary, these results support the use of RBCs as an antigen delivery system for a powerful cancer immunotherapy approach.