I. Delivery of carbohydrate antigens by glycopolymers as potential anti-cancer vaccines : II. A study of the impacts of valency and density on immune response against a tumor associated carbohydrate antigen
Tumor associated carbohydrate antigens (TACAs) are overexpressed on tumor cells, which renders them attractive targets for anti-cancer vaccines. To overcome the poor immunogenecity of TACAs, a polymer platform was designed for antigen presentation by taking advantage of the polymeric backbone to deliver TACA and helper T (Th) cell epitope on the same chain. The block copolymer was synthesized by cyanoxyl-mediated free radical polymerization followed by conjugation with a TACA Tn antigen and a mouse Th-cell peptide epitope derived from poliovirus (PV) to afford the vaccine construct. The glycopolymer vaccine elicited a robust immune response with significant titers of IgG antibodies and the antibodies generated recognized Tn antigens on tumor cell surface. For successful carbohydrate based anti-cancer vaccines, it is critical that B cells are activated to secret antibodies targeting TACAs. Despite the availability of many TACA based constructs, systematic understanding of the effects of structural features on anti-glycan antibody responses is lacking. In this study, a series of defined synthetic glycopolymers bearing a representative TACA, i.e., the Thomsen-nouveau (Tn) antigen, have been prepared to probe the induction of early B cell activation and antibody production via a T cell independent mechanism. Valency and density of the antigen in the polymers turned out to be critical. An average of greater than 6 Tn per chain was needed to induce antibody production. Glycopolymers with 40 antigens per chain and backbone molecular weight of 450 kDa gave the strongest stimulation to B cells in vitro, which correlated well with its in vivo activity. Deviations from the desired valency and density led to decreased antibody production or even antigen specific B cell non-responsiveness. These findings provide important insights on how to modulate anti-TACA immune responses facilitating the development of TACA based anti-cancer vaccines using glycopolymers.
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- In Collections
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Electronic Theses & Dissertations
- Copyright Status
- In Copyright
- Material Type
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Theses
- Authors
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Qin, Qian, 1981-
- Thesis Advisors
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Huang, Xuefei
- Date
- 2019
- Program of Study
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Chemistry - Doctor of Philosophy
- Degree Level
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Doctoral
- Language
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English
- Pages
- xxv, 159 pages
- ISBN
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9780438792036
0438792033
- Permalink
- https://doi.org/doi:10.25335/dfsy-2q15