In the cancer setting, exosomes have been described to play immunomodulatory roles2,3. Immune cells, such as dendritic cells, as well as cancer cells release exosomes with immunoactive properties. For example, exosomes can carry tumor antigens, which activate CD4+ and CD8+ T cells of the adaptive immune system. Or, exosomes may carry immunosuppressive proteins such as CTLA4, PD-L1, CD39, and CD73, thereby promoting tumor immune escape and tumor progression. Exosomes are also being evaluated as a prognostic biomarker in some human cancers, including sarcoma4. This is because tumor-derived exosomes contain components of the tumor cell from which they were derived, but can be noninvasively sampled from blood and other body fluids. Exosomes appear to be a negative prognostic marker in several types of cancer including sarcoma and melanoma4,5. In melanoma, a phenomenon has been described in which melanoma-derived exosomes arrive at the tumor-draining lymph node, where they prime the lymph node to be hospitable to tumor cells through increased vascularization and extracellular matrix deposition5.
Most recently, there has been a renewed interest in exosomes due to their utility as a drug delivery mechanism. Exosomes can be used to deliver nucleic acids such as DNA or microRNA6, or drugs/small molecules, in the therapeutic setting. Similar biologic delivery mechanisms are already in use, including encapsulating drugs in liposomes or protein-based nanoparticles4. A major advantage of using exosomes as compared to existing biologic delivery mechanisms is that the coat of the exosome determines its targeting in the body7. Several subtypes of exosomes are being evaluated for drug delivery purposes. Firstly, the targeting of naturally-derived exosomes based on the composition of proteins in its coat has been established, so synthetic exosomes with engineered coats are one therapeutic possibility that removes any variability between naturally-occurring exosomes while preserving one major advantage to exosomes as a delivery mechanism8. Secondly, there are multiple mechanisms by which exosomes can be loaded with cargo9. Cargo may be loaded into purified exosomes, or cells in culture can be loaded with small molecules or nucleic acids that will be packaged into exosomes in culture, and then loaded exosomes purified.
Bethyl's PathPlex® multiplex antibodies work with many of the targets associated with Exosome research.
