Increasing vaccine potency through exosome antigen targeting.

While many tumor associated antigens (TAAs) have been identified in human cancers, efforts to develop efficient TAA "cancer vaccines" using classical vaccine approaches have been largely ineffective. Recently, a process to specifically target proteins to exosomes has been established which takes advantage of the ability of the factor V like C1C2 domain of lactadherin to specifically address proteins to exosomes. Using this approach, we hypothesized that TAAs could be targeted to exosomes to potentially increase their immunogenicity, as exosomes have been demonstrated to traffic to antigen presenting cells (APC).

Targeting tumor antigens to secreted membrane vesicles in vivo induces efficient antitumor immune responses.

Expression of non-self antigens by tumors can induce activation of T cells in vivo, although this activation can lead to either immunity or tolerance. CD8+ T-cell activation can be direct (if the tumor expresses MHC class I molecules) or indirect (after the capture and cross-presentation of tumor antigens by dendritic cells). The modes of tumor antigen capture by dendritic cells in vivo remain unclear.

Exosomes as novel therapeutic nanodevices.

Exosomes are small vesicles (60 to 100 nm) that are released by many cell types. Their heterogeneous protein and lipid compositions, in addition to their enduring physicochemical features have led to the idea of using these natural vesicles as nanodevices for the development of new therapeutic applications. The first exosome-based nanodevices evaluated in the clinic consisted of autologous dexosomes (patient-specific exosomes released by dendritic cells and loaded with tumor antigen-derived peptides).

Exosome Display technology: applications to the development of new diagnostics and therapeutics.

Exosome Display is a novel methodology enabling the manipulation of exosome protein content. This technology stems from the identification of addressing domains that mediate the specific distribution of proteins on exosomes. More particularly, Lactadherin expressed in non-mammary gland tissue has been found to localize to exosomes via binding of its C1C2 domain to exosome lipids.