Immunotherapy with dendritic cell nanovesicles
Dongbin Jin and Jonathan Sprent. Garvan Institute of Medical Research, Sydney, Australia

Interest in cancer immunotherapy has been bolstered by the recent success of T cell checkpoint (PD-1) blockade with specific antibodies. This approach might be especially effective if combined with methods for enhancing tumor immunogenicity, eg injection of dendritic cells (DC) expressing tumor antigens. Currently, DC therapy is successful in only a small proportion of patients, perhaps reflecting poor homing of injected DC. To overcome this problem, we have generated cell-surface membrane nanovesicles from in vitro-generated bone-marrow-derived mature DC. When loaded with specific peptide, the vesicles are stimulatory for naïve TCR transgenic CD8 T cells in vitro without APC, though only with aggregated vesicles and not with vesicles dispersed into nano-vesicles by sonication. By contrast, after IV injection in vivo, the nanovesicles are much more immunogenic than aggregates and generate strong proliferation and effector function of CD8 cells in both spleen and LN, reflecting widespread distribution of the vesicles and uptake by host APC. Preliminary work has shown that injection of the vesicles can be used to reject established tumours in mice.
Date: 11 May 2016, 1:30 (Wednesday, 3rd week, Trinity 2016)
Venue: MRC Weatherall Institute of Molecular Medicine, Headington OX3 9DS
Venue Details: Seminar Room
Speaker: Prof Jonathan Sprent (Garvan Institute of Medical Research, Sydney)
Organising department: MRC Human Immunology Unit
Organiser: Anne Farmer (MRC Human Immunology Unit)
Organiser contact email address:
Host: Georg Hollander
Part of: MRC TIDU Wednesday Seminar Series
Booking required?: Not required
Audience: Members of the University only
Editor: Anne Farmer