Ar vesicle-encapsulated oncolytic adenoviruses for enhanced therapeutic impact Heikki Saari1, Mariangela Garofalo1, Petter Somersalo1, Laura Aksela2, Elisa L aro-Ib ez1, Matti Jalasvuori3, Tatu Rojalin4, Vincenzo Cerullo5, Lukasz Kuryk6 and Marjo Yliperttula1 Division of Pharmaceutical Biosciences, Centre for Drug Study, Faculty of Pharmacy, University of Helsinki, Finland; 2Orion Corporation; 3Biological and Enviromental Science, University of Jyv kyl Finland; 4University of Helsinki, Finland; 5Laboratory of ImmunoVirothetherapy, Centre for Drug Study, Faculty of Pharmacy, University of Helsinki, Finland; 6Laboratory of ImmunoVirotherapy, Centre for Drug Reserach, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, FinlandPS02.MHC mismatch in exosomal cancer immunotherapy paving the way for allogeneic exosome treatment Pia Larssen1, Rosanne Veerman2, Stefanie Toll Like Receptor 10 Proteins Source Hiltbrunner2, Mikael Karlsson3 and Susanne GabrielssonKarolinska Institutet; 2Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; 3Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Stockholm, SwedenExosomes are fascinating as potential cancer immunotherapy vehicles because of their capacity to potentiate immune responses and stimulate tumour-specific immune activation in mice. Even so, previous clinical trials with peptide-loaded autologous exosomes only showed moderate T cell responses in humans, suggesting that exosome-induced immunity is still not totally understood. We recently demonstrated that antigen-specific CD8+ T cell responses are independent of significant histocompatibility complex (MHC) class I presence on exosomes. In addition, exosomes lacking MHC class I, as well as exosomes with each MHC class I and II mismatch, are equally effective in inducing antigen-specific tumour-infiltrating T cells inside a B16 melanoma model as autologous exosomes. Still, the impact of several injections of allogeneic exosomes has not yet been investigated. We here show that repeated injections of OVA loaded exosomes induce far more germinal centre B cells and boost antigen-specific antibody production, therefore providing an adjuvant effect in vivo. Moreover, the impact of repeated injections on tumour clearance in the B16-OVA melanoma model is at present beneath investigation. In EphA3 Proteins Source conclusion, our information show that booster injections of allogeneic exosomes outcome in enhanced antigen-specific CD8+ T cell, germinal centre B cell, and follicular T helper cell responses, also as improved antigen-specific antibodies. Importantly, our findings assistance the application of allogeneic exosomes for therapeutic use in humans.Introduction: Oncolytic viruses are a promising future treatment option for cancer, even so, their use in therapy is limited as a consequence of their immune reactivity and requirement towards certain receptors around the surface of your cells to become infected. Here we’ve studied the possibility of encasing the virus inside extracellular vesicles (EVs) as a way to circumvent these limitations by each shielding them from any interactions with immune cells and giving alternative mechanisms for cellular uptake. Strategies: EV-encapsulated oncolytic adenoviruses were ready by infecting cancer cells together with the virus. When the cells have been observed to be dead EVs were isolated from the cell culture medium by ultracentrifugation followed by overnight gradient centrifugation inside a linear sucrose gradient. 1 mL fractions w.