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 Analysis, 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 remedy Pia Larssen1, Rosanne Veerman2, Stefanie Hiltbrunner2, Mikael Karlsson3 and Susanne GabrielssonKarolinska Institutet; 2Immunology and Allergy Unit, Division of Medicine, Karolinska Institutet, MMP-14 Storage & Stability Stockholm, Sweden; 3Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Stockholm, SwedenExosomes are fascinating as possible cancer immunotherapy cars as a result of their capacity to potentiate immune responses and stimulate tumour-specific immune activation in mice. Nonetheless, previous clinical trials with peptide-loaded autologous exosomes only showed moderate T cell responses in humans, suggesting that exosome-induced immunity is still not completely understood. We not too long ago demonstrated that antigen-specific CD8+ T cell responses are independent of significant histocompatibility complicated (MHC) class I presence on exosomes. Furthermore, exosomes lacking MHC class I, too as exosomes with both MHC class I and II mismatch, are equally effective in inducing antigen-specific tumour-infiltrating T cells within a B16 melanoma model as autologous exosomes. Nonetheless, the effect of several injections of allogeneic exosomes has not but been investigated. We right here show that repeated injections of OVA loaded exosomes induce more germinal centre B cells and enhance antigen-specific antibody production, as a result providing an adjuvant effect in vivo. Additionally, the impact of repeated injections on tumour clearance within the B16-OVA melanoma model is at the moment under investigation. In conclusion, our data 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 enhanced antigen-specific antibodies. Importantly, our findings support the application of allogeneic exosomes for therapeutic use in humans.Introduction: Oncolytic viruses are a promising future remedy solution for cancer, nevertheless, their use in therapy is limited because of their immune reactivity and requirement towards precise receptors around the surface with the cells to become infected. Right 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 PARP Inhibitor drug interactions with immune cells and providing option mechanisms for cellular uptake. Strategies: EV-encapsulated oncolytic adenoviruses had been ready by infecting cancer cells together with the virus. When the cells were observed to become dead EVs were isolated in the cell culture medium by ultracentrifugation followed by overnight gradient centrifugation within a linear sucrose gradient. 1 mL fractions w.
