Uction of hybrids EVs with new properties like PEGylated EVs and/or drug-loaded EVs. This process is combined to a new higher yield approach for production and loading of neutral precursor liposomes. Benefits: The liposome production technique makes it possible for encapsulation of as much as 80 of practically any hydrophilic or lipophilic compounds like sulforhodamine B, Vitronectin Proteins Storage & Stability inorganic 50-nm nanoparticles, siRNA or fluorescent lipids into 5000-nm neutral liposomes. According to fusion parameters and liposome composition, PEG-facilitated fusion of EVs with liposomes enables the transfer to mesenchymal stem cells-derived EVs of up to 95 from various liposomal lipophilic drugs or functionalized lipids and 40 from hydrophilic inner compounds (rhodamine/siRNA). The resulting UCH Proteins Recombinant Proteins hybrid EVs maintain their endogenous biological activity and display further tunable functionalities coming from liposomes.Saturday, 05 May well 2018 Research Institute, Department of Cancer Biology and Genetics, College of Medicine; The Ohio State University, Columbus, USAHybrid EVs display a three- to fourfold boost in tumour cell internalization when compared with precursor liposomes in vitro with connected improve within the therapeutic effect using an FDA-approved photosensitizer agent (Foscan) as light-activated therapeutic cargo. In vivo biodistribution patterns show improved accumulation in tumours in comparison with wholesome tissues in an orthotopic peritoneal carcinomatosis mouse model. Therapeutic studies are ongoing. Summary/Conclusion: EV/liposome fusion, coupled to higher yield production of drug-loaded neutral liposomes, allows to enhance the EV loading efficiency even for hydrophilic drugs, rendering feasible the democratization and standardization of EV-based drug delivery systems.OS24.Allogenicity boosts exosome-induced antigen-specific humoral and cellular immunity and mediate long-term memory in vivo Susanne Gabrielsson; Pia Larssen; Rosanne Veerman; G de Gucluler; Stefanie Hiltbrunner; Mikael Karlsson Karolinska Institutet, Stockholm, SwedenBackground: Exosomes are interesting as prospective cancer immunotherapy cars due to their capacity to stimulate tumour-specific activity in mice. Nonetheless, clinical trials applying peptide-loaded autologous exosomes showed only moderate T cell responses, suggesting a have to have for optimization of exosome-induced therapy in humans. We previously demonstrated that the presence of antigen-specific CD8+ T cells and antitumour responses to whole antigen have been independent of major histocompatibility complicated on exosomes and hypothesized that repeated injections of allogeneic exosomes would potentiate antigen-specific responses. Strategies: Allogeneic or syngeneic exoxomes derived from bone-marrow-derived dendritic cells have been injected when or twice into C57BL/6 mice, and immune responses had been measured by flow cytometry, ELISA and ELISPOT. Exosomes were analysed by electron microscopy, NanoSight, fluorescence-activated cell sorting, Western blot and ELISA. Exosomes have been also given as treatment inside the B16 melanoma model. Results: Two injections of allogeneic exosomes enhanced antigen-specific CD8+ T cell, germinal center B cell and follicular helper T cell and antigen-specific antibody responses in comparison to syngeneic exosomes. Exosome-injected mice demonstrated antigen-specific memory after 4 months, with highest antibody avidity in mice getting double allogeneic exosome injections. Additionally, allogeneic exosomes had been far more potent than syngeneic to delay cancer progression within a melan.
