Research

Immunotherapy

Peptide amphiphiles can form versatile macromolecular constructs that have tremendous potential for immunotherapeutic applications. In specific, peptide amphiphiles undergo self-assembly into micelles of a variety of shapes which allow for the multivalent presentation of peptides, the formation of peptide secondary structures often only seen with full proteins, and the co-deliver non-specific immune boosting substances termed adjuvants. These beneficial attributes combined with the nanoscale dimensions of micelles make it possible for these peptide delivery vehicles to efficiently enter the lymphatic system, be passively targeted to lymphocytes in the regional draining lymph nodes, and induce a strong immune response specific to the peptide displayed in the peptide amphiphile.

Peptide Amphiphile Vaccines

Artistic rendering of a peptide amphiphile vaccine. Image courtesy of Peter Allen.

Several projects are ongoing that aim to assess the feasibility of using peptide amphiphile micelles for immunological applications. The capacity to create prophylactic vaccines has been extensively studied with peptide amphiphile micelles being shown capable of generating cytotoxic T cell response to model tumor antigens that can delay solid tumor growth and producing antibody responses against streptococcal bacteria in vivo. Our laboratory is currently collaborating with Prof. Maciej Lesniak at the University of Chicago and Prof. Michael Federle at the University of Illinois at Chicago to further study the cancer and streptococcal vaccines, respectively. A new project with Prof. Joel Collier and Prof. Robert Daum at the University of Chicago has recently been initiated to utilize our peptide amphiphile micelle technology as a staphylococcal vaccine delivery system. In addition to investigating the prophylactic vaccine applications of peptide amphiphile micelles, a variety of therapeutic immunological applications of these materials are also being explored. One particularly exciting new collaborative project with Prof. James LaBelle is studying the potential to utilize peptide amphiphile micelles to transiently kill regulatory T cells which can enhance the effectiveness of the anti-cancer host immune response as well as traditional chemotherapy regimens.

References

  • "Self-Assembled Peptide Amphiphile Micelles Containing a Cytotoxic T-Cell Epitope Promote a Protective Immune Response In Vivo," M. Black, A.Trent, Y. Kostenko, J.S. Lee, C. Olive, and M. Tirrell, Advanced Materials, 24, 3845–3849 (2012). [PDF]
  • "Toll-like receptor-mediated adjuvanticity and immunomodulation in dendritic cells: Implications for peptide vaccines," D. Mitchell, M. Yong, J. Raju, N. Willemsen, M. Black, A. Trent, M. Tirrell, and C. Olive, Human Vaccines, 7, 85-93. (2011). [PDF]
  • “Advances in the Design and Delivery of Peptide Subunit Vaccines with a Focus on Toll-Like Receptor Agonists”, M. Black, A. Trent, M. Tirrell and C. Olive, Expert Review of Vaccines, 9, 157-173 (2010). [PDF]

Funding

Collaborators