PCI-based vaccination: a novel method for targeting of MHC class I antigen presentation and stimulation of antigen-specific cytotoxic T cells

Abstract

Abstract Cytotoxic CD8+ T cells are key players in fighting cancer and infectious diseases, hence, the design of therapeutic vaccines focuses on ways to prime strong cytotoxic immune responses. Yet, current vaccines efficacy is limited mainly due to the default processing of exogenous antigens via the MHC class II pathway and the activation of CD4+ and not CD8+ T cells. Photochemical internalization (PCI) is a novel intracellular delivery approach, able to circumvent the MHC class II processing. Briefly, after endocytosis of antigen and photosensitizer by antigen presenting cells, light activation of the photosensitizer causes disruption of endosomal membrane and antigen release into the cytosol, resulting in stimulation of MHC class I-restricted CD8+ T cells. Wild type and MHC class II-deficient mice were immunized intradermally with protein antigens and photosensitizer, followed by controlled light exposure for activation of the photosensitizer. The effectiveness of the PCI to stimulate CD8+ T cells was analyzed by measuring frequency, phenotype, and function of antigen-specific T cells in blood and spleens. PCI-treated mice showed a strong activation and proliferation of specific CD8+ T cells, with improved functions in terms of IFN-g production and cytotoxic capacity. The CD8+ T cell effector functions were not impaired in MHC class II-deficient or in CD4+ T cell-depleted mice, suggesting that the PCI-mediated antigen processing is independent of MHC class II and CD4+ T helper cells. Our data demonstrate that PCI–based vaccination can stimulation strong and functional cytotoxic CD8+ T cells, making PCI a potential method for use in therapeutic vaccines against cancer and infectious diseases.