ChE Pirkey Centennial Lecture – “Glycomaterials for Engineering Immunity and Tolerance” by Dr. Jeffrey Hubbell (University of Chicago)
Host: Dr. Adrianne Rosales; 2017-2018 Pirkey Lectureship
Adaptive immune responses are triggered particularly powerfully in the lymph nodes and in the lymphoid tissues associated with mucosae. We are developing nanomaterials and soluble polymers to exploit interstitial flow from the site of administration to the lymph nodes, using the material vectors to carry both antigen and adjuvant biomolecules. We are particularly interested in therapeutic vaccination, which requires induction of CD8 T cell responses in addition to humoral responses. Using both biophysical factors and biochemical recognition to target dendritic cells resident in the lymph nodes is particularly interesting. Among biochemical recognition, we are exploring glycopolymers to target lectin receptors on the surfaces of immune cells resident in the injection site-draining lymph nodes as a vaccine platform.
In addition to inducing adaptive immune responses, so-called inverse vaccination to induce antigen-specific tolerance is of high interest. We are exploring biological approaches to deliver protein antigens in a tolerogenic manner, including targeting antigen to the surfaces of erythrocytes after injection, based on the premise that aged erythrocytes are cleared tolerogenically, along with exogenous antigen cargo they may carry. We have shown the ability to induce antigen-specific anergy as well as T regulatory responses, working in models of autoimmunity and of immune response to protein drugs. In this work, the liver appears to be a particularly interesting target for antigen delivery, and we are accordingly exploring glycopolymers to target particular lectin receptors in liver cells in autoimmune and protein drug applications.
Jeffrey Hubbell is Professor in the Institute for Molecular Engineering of the University of Chicago. Previous to moving to Chicago, he was on the faculty of the Swiss Federal Institute of Technology Lausanne (EPFL, where he served as Director of the Institute of Bioengineering and Dean of the School of Life Sciences), the Swiss Federal Institute of Technology Zurich and University of Zurich, the California Institute of Technology, and the University of Texas in Austin. He holds a BS from Kansas State University and a PhD from Rice University, both degrees being in chemical engineering. He was elected to the US National Academy of Engineering in 2010 and the National Academy of Inventors in 2014.
Hubbell uses biomaterials and protein engineering approaches to investigate topics in regenerative medicine and immunotherapeutics. In regenerative medicine, he focuses on biomaterial matrices that mimic the extracellular matrix and on growth factor – extracellular matrix interactions, working in a variety of animal models of regenerative medicine. In immunotherapeutics, he focuses on nanomaterials in vaccines that target lymphoid-resident antigen presenting cells and on protein engineering approaches to deliver antigen to the spleen and liver for inverse vaccines to induce tolerance to protein drugs and in autoimmunity. His interests are both basic and translational, having founded or co-founded five biomedical companies based on his technology, namely Focal, in Boston, acquired by Genzyme; Kuros Biosciences, in Zurich, in the domain of regenerative medicine; Anokion and Kanyos Bio, in Boston, both in the domain of immunological tolerance; and Clostra Bio, in Chicago, in the domain of food allergy.