Synergistic induction of anti-tumour immunity by co-delivery of protein and α-galactosylceramide on exosomes (P4457)

• Main Authors: Gehrmann, Ulf, Hiltbrunner, Stefanie, Georgoudaki, Anna-Maria, Karlsson, Mikael C., Näslund, Tanja I., Gabrielsson, Susanne
• Format: Conference Proceeding
• Language: English
• Subjects: Medicin och hälsovetenskap
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.190.Supp.126.12

Exosomes, nanosized endogenous vesicles, can induce adaptive immune responses and have been tested in cancer treatment. Similarly, the iNKT cell ligand α-galactosylceramide (αGC) presented on the MHC class I-like molecule CD1d has been used for therapeutic purposes in cancer trials. Here, we investigated if exosomes can be loaded with αGC to activate iNKT cells and potentiate a cancer-specific adaptive immune response. We show that αGC loaded exosomes readily activate iNKT cells both in vitro and in vivo. In addition, exosomes loaded with αGC and the model antigen ovalbumin (OVA) induced a potent NK and γδ T cell innate immune response, followed by synergistically amplified T and B cell responses. Interestingly, αGC/OVA-loaded exosomes did not induce iNKT cell anergy, in contrast to soluble αGC, and were more potent than soluble αGC and OVA in inducing adaptive immunity. Finally, tumor-bearing mice treated with αGC/OVA-loaded exosomes displayed decreased tumor growth and increased T cell tumor infiltration in comparison to mice immunized with OVA-loaded exosomes in an OVA-specific mouse melanoma model. These results show that exosomes loaded with protein antigen and the glycolipid αGC effectively activate both innate and adaptive immunity, important for future cancer immunotherapy design.