Proposed effects of exosome depletion on the activity of therapeutic antibodies in cancer.
(A) Tumor-secreted exosomes display oncoproteins from their originating tumor cell. This example depicts HER2 over-expressing tumor cells releasing HER2+ exosomes that promote tumor growth and immune suppression, as described in [99–101]. (B) Monoclonal antibodies administered for immunotherapy can be sequestered by tumor-derived exosomes, owing to the display of oncogenic proteins on the exosomal surfaces [99–101, 114]. In this example, HER2+ exosomes bind to anti-HER2 antibodies (for example, Herceptin®) and limit the bioavailability of antibodies. Consequently, continued tumor growth is permitted via interactions between HER proteins on the surfaces of tumor cells (consisting of dimers of HER2 with another HER family member), and growth factors/EGFR ligands in the tumor microenvironment. (C) A strategy for therapeutic filtration of exosomes from the circulation (shown here) or pharmacological methods of targeting exosome release by cancer cells could enhance the efficacy of immunotherapy. Conceptually, removal of exosomes from the bloodstream would allow therapeutic anti-HER2 antibodies to block HER-related signaling on tumor cells, thereby also alleviating exosome-mediated immune suppression and other pro-cancer activities.