@article{Applications:7593,
      recid = {7593},
      author = {Alpar, Aaron Tamas},
      title = {Cytokine Engineering to Modulate DC:Treg Networks and  Therapeutic Applications Thereof},
      publisher = {The University of Chicago},
      school = {Ph.D.},
      address = {2023-08},
      pages = {170},
      abstract = {This thesis serves to explore engineering mechanisms by  which dendritic cells and their interactions are capable of  modulating immune responses. In this, I explore the  generation, characterization, and use of a novel cytokine  fusion, Flt3L-SA, to therapeutic ends involving both the  innate and adaptive immune system. Chapter 1 defines the  major players of the immune system. Herein I also explore  how these cellular and soluble factors interact and play  off of one another to generate beneficial immune responses  (pro- and anti-inflammatory) as well as characterize when  an immune response malfunctions and the issues it may  cause. Finally, I review past and future protein- based  technologies involved in immunomodulation to skew immune  responses back in an appropriate direction in instances  such as pushing inflammation forward to generate anti-  tumor immunity, or skewing away from pathogenic  inflammation to an inert form. In Chapter 2, I introduce my  novel engineered-cytokine. The fusion of Flt3L to serum  albumin (called Flt3L-SA), is then rigorously characterized  for binding, activity, and pharmacokinetics and dynamics.  We here explore how treatment impacts players of both the  adaptive and innate systems with an obvious focus on  Dendritic Cells, but also how this expansion of DCs impacts  the T cell compartments, primarily that of Tregs. Following  the general characterization of treatment with Flt3L-SA,  Chapter 3 explores the utility of such a treatment in many  settings. The first setting this is characterized in is the  use of Flt3L-SA with an immunogenic protein drug as a model  of enzyme replacement therapy and the prevention of  antibodies to the foreign drug. Furthermore, as we note a  major immune skewing in the immune system related to the  gut, we also explore how oral antigen treatment in  combination with Flt3L-SA changes the context in which  immune education occurs. Finally, Chapter 4 discusses  future works involving this fusion protein in tolerance and  wound healing.},
      url = {http://knowledge.uchicago.edu/record/7593},
      doi = {https://doi.org/10.6082/uchicago.7593},
}