(526h) Oncofetal Antigen Peptide Nanoclusters for Cancer Vaccines
AIChE Annual Meeting
2017
2017 Annual Meeting
Materials Engineering and Sciences Division
Biomaterials for Immunological Applications I: Immune Activation and Vaccination
Wednesday, November 1, 2017 - 2:36pm to 2:54pm
To enable optimal particle fabrication from OFA 2, it was modified with the addition of one cysteine onto the C-terminus, making OFA 2C. Desolvation was used to make nanoclusters ~200 nm in diameter, consisting of OFA 2C crosslinked with a thiol crosslinker. Peptide concentration, solvent:desolvent pairings and volume ratio, crosslinker type and concentration were among the parameters optimized in nanocluster synthesis to achieve a target size to maximize dendritic cell antigen recognition and uptake as well as to minimize passive diffusion away from the injection site prior to uptake. A reversible thiol crosslinker was used to maintain the immunogenic epitope sequence after intracellular processing and breakdown of the nanocluster. OFA 2C nanoclusters demonstrated comparable dendritic cell (DC) uptake in vitro in comparison to OFA 2C peptide administered in soluble form. DC activation and surface presentation of internalized peptide nanoclusters, however, has shown to be enhanced compared to soluble peptide. In an in vivo mouse model, the nanoclusters were retained 2.7-fold more in an intradermal injection site (an area high in localized immune cell uptake and trafficking) than the injected soluble peptide. Ongoing work is assessing any benefits in nanocluster presentation and activation of T-cells by DCs compared to soluble peptides. The peptide nanocluster formation of immunogenic peptide OFA 2C holds potential to increase the efficacy of OFA cancer vaccines.
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