Exosomes are nano-sized vesicles secreted by cells that contain proteins, RNAs, polysaccharides, and lipids, playing a key role in cellular communication and holding promise for diagnostic and therapeutic applications. Tumor-derived exosomes facilitate tumor progression and metastasis by transporting molecular messages and contribute to the immunosuppressive tumor microenvironment. They can penetrate blood vessels and circulate in the bloodstream, making them potential markers for cancer diagnosis. Exosomes also serve as a source of tumor antigens for cancer vaccines, which aim to generate antigen-specific immune responses. However, identifying tumor-specific antigens is complex and costly. Tumor exosome-based vaccines have shown promise in clinical trials but face challenges in effectively activating dendritic cells (DCs) and generating strong cytotoxic T lymphocyte (CTL) responses. The integration of adjuvants with tumor exosomes has not significantly improved vaccine potency due to differing trafficking and uptake profiles. There is a need for effective methods to conjugate adjuvants to exosomes to enhance their synergistic effects.
This technology is a method for development of personalized cancer vaccines using cancer cell-derived exosomes. Cancer cells collected from a patient can be labeled with unnatural sugars displaying the azide functional group. Exosomes generated from these cancer cells can be conjugated to adjuvants (or other tags or fluorescent dyes for diagnostic or research purposes) via click chemistry and reintroduced into the patient. Components of the exosome can be recognized as antigens and help the immune system in producing antigen-specific T cells and antibodies, showing a lower concentration of adjuvant is required to trigger the immune response.
Benefits
Conjugating adjuvant to exosomes improves immune response against cancer cells.
Lower concentration of potentially toxic adjuvant is required to trigger the immune response.
Publication
Bhatta, R., Han, J., Liu, Y. et al. Metabolic tagging of extracellular vesicles and development of enhanced extracellular vesicle based cancer vaccines. Nat Commun 14, 8047 (2023). https://doi.org/10.1038/s41467-023-43914-8