Design and Characterization of Self-Assembling, Peptide-Based Biomaterials As Immunotherapeutics

With the goal of exploring strategies for the rational design of immunotherapeutics, we propose using peptide amphiphile (PA) molecules as building blocks for novel peptide antigen delivery systems. PAs can form versatile macromolecular constructs that combine the biofunctionality of peptides with a controllable self-assembly character obtained by synthetic chemical conjugation of peptide head groups with hydrophobic hydrocarbon tails (i.e. a fatty acid). In aqueous conditions, the hydrophobic effect drives PAs to self assemble into hierarchical structures, including spherical, cylindrical and worm-like micelles. PAs confer a number of attractive properties for peptide-based immunotherapy, including the multivalent presentation of peptide antigens, the enhanced peptide secondary structure often seen upon aggregation, and the potential of the hydrophobic tails to act as adjuvants. Peptides derived from the model tumor antigen ovalbumin and from an antigenic sequence found in Group A Streptococcus have been incorporated into two different PA vaccines. Their physical characterization, as well as their immunogenicity both in vitro and in mouse studies will be presented.