Self Assembling Peptide Amphiphes As An Alternate Aproach to Immunotherapy

Peptides are capable of stimulating an immune response but are generally weak immunogens on their own and require strong adjuvants to be effective, prohibiting their use in clinical applications. Peptide amphiphiles (PAs), which consist of a hydrophilic peptide conjugated to a hydrophobic lipid or fatty acid tail, self assemble into micelles that we propose have distinct advantages for a safe and effective antigen delivery system. PA micelles display a high density of peptide antigen and can be efficiently taken up by immune cells. Multiple functionalities can be incorporated into the micelles in a modular fashion by simple mixing of the different molecules, alleviating the need for complex chemistries to covalently link different components. Two different PA vaccines have been developed to evaluate the potential of PA micelles to serve as a platform for immunotherapy. PAs containing a cytotoxic T-cell (T_c-cell) epitope derived from the model tumor antigen ovalbumin stimulate a T_c-cell response, providing protection in mice against tumor growth. Other PAs incorporating an antigenic sequence found in Group A Streptococcus induce a potent antibody response in mice. The antibody response was further enhanced by using amphiphilic Toll-like receptor agonists to make mixed micelles. The design and physical characterization of the PA micelles will be discussed, along with details regarding their in vivo immunogenicity.