Increasing vaccine potency through exosome antigen targeting
Open accessAbstract
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). To investigate this possibility, we created adenoviral vectors expressing the extracellular domain (ECD) of two non-mutated TAAs often found in tumors of cancer patients, carcinoembryonic antigen (CEA) and HER2, and coupled them to the C1C2 domain of lactadherin. We found that these C1C2 fusion proteins had enhanced expression in exosomes in vitro. We saw significant improvement in antigen specific immune responses to each of these antigens in naïve and tolerant transgenic animal models and could further demonstrate significantly enhanced therapeutic anti-tumor effects in a human HER2+ transgenic animal model. These findings demonstrate that the mode of secretion and trafficking can influence the immunogenicity of different human TAAs, and may explain the lack of immunogenicity of non-mutated TAAs found in cancer patients. They suggest that exosomal targeting could enhance future anti-tumor vaccination protocols. This targeting exosome process could also be adapted for the development of more potent vaccines in some viral and parasitic diseases where the classical vaccine approach has demonstrated limitations.
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DC-derived exosomes gain MHC-I that combines with tumor-derived peptides, and the complex could activate NK or T cells to suppress tumors.
“Notably, DC-derived exosomes gain MHC-I that combines with tumor-derived peptides, and the complex could activate NK or T cells to suppress tumors [45,46].”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [45]
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- Authors
- Hartman, Z. C., Wei, J., Glass, O. K., Guo, H., Lei, G., Yang, X.-Y., Osada, T., Hobeika, A., Delcayre, A., Le Pecq, J.-B., Morse, M. A., Clay, T. M., & Lyerly, H. K.
- Affiliations
- Duke University (US)
- Corresponding author
- Lyerly, Herbert K.
- ORCID
- Venue
- Vaccine
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 29
- Issue
- 50
- Pages
- 9361-9367
- ISSN
- 0264-410X (ISSN-L)
- PMC
- PMC3350974
- OpenAlex
- W1992571832
- Cited by
- 196
- References
- 26
- Citations by year
- 2026: 1 · 2025: 11 · 2024: 13 · 2023: 19 · 2022: 18 · 2021: 15 · 2020: 14 · 2019: 21 · 2018: 14 · 2017: 11 · 2016: 10 · 2015: 12 · 2014: 22 · 2013: 8 · 2012: 7
- FWCI
- 5.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Vaccine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Susan G. Komen (KG080627)
- U.S. Department of Defense (BC050221)
- National Cancer Institute (R01 CA95447, P50 CA89496-01)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- exosome targeting, tumor-associated antigens, cancer vaccines, carcinoembryonic antigen, HER2, adenoviral vector, antigen immunogenicity, antigen-presenting cells, antitumor immunity, transgenic animal models
- MeSH terms
- Adenoviridae, Animals, Antigen-Presenting Cells, Antigens, Surface, Carcinoembryonic Antigen, Genetic Vectors, Humans, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Milk Proteins, Neoplasms, Recombinant Fusion Proteins, Erb-b2 Receptor Tyrosine Kinases, Cancer Vaccines, Cell Line, Tumor, Mice, Exosomes
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