Immunoengineering promises to yield the next generation of therapies for unmet medical needs in infectious disease, autoimmunity, and cancer. A key challenge in the immunoengineering field is our limited understanding of how the immune system recognizes and responds to glycoconjugates. Glycoconjugates – biopolymers decorated with sugars, or glycans – coat the surface of every cell and play central roles in immunology. For example, glycoconjugates regulate immune cell trafficking, modulate immune cell activation, and represent molecular patterns that define self and non-self. The chemical structures of appended glycans are often altered in disease states and can contribute to pathogenesis by modulating immune responses. Thus, glycoconjugates represent a vast set of attractive, yet mostly untapped, disease-specific antigens and targets for immunotherapy. My work has resulted in a suite of high-throughput and modular technologies for elucidating and engineering the immune response to glycoconjugates. I engineered a cell-free technology for on-demand and portable production of glycoconjugate vaccines (Stark et al. Sci Adv 2020). Cell-free synthesized vaccines protected mice from lethal pathogen challenge via induction of glycan-specific immune responses. My cell-free approach can further be used for rapid and facile biosynthesis of glycoproteins bearing a variety of user-specified glycan structures, which promises to accelerate interrogation of their immunomodulatory properties (Jaroentomeechai & Stark et al. Nat Commun 2018). My current work focuses on identifying and targeting glycoconjugates that allow cancer cells to evade anti-tumor immune responses. Specifically, I developed a new class of antibody-lectin bispecifics for blockade of glyco-immune checkpoints that enhance anti-tumor immune responses in vitro (Stark et al. in prep). The bispecific platform is modular and can be applied to diverse disease- or cell type-specific antigens and lectin (glycan-binding) immunoreceptors. In parallel, I established an interaction proteomics pipeline to define tumor-associated glycoconjugates that engage inhibitory glycan-binding immunoreceptors called Siglecs, revealing new targets for cancer immunotherapy (Stark et al. in prep). Collectively, my work has helped elucidate the roles of immunomodulatory glycoconjugates in disease and promises to accelerate development of new vaccines and immunotherapies.

Engineering (Glyco)immunology

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.