(Georgia Institute of Technology, 2022-05)
Holzworth, Peyton
Cancer is among the leading causes of death worldwide; in 2018, there were 18.1 million new cases and 9.5 million cancer-related deaths. Current methods, such as chemotherapy, have been used for decades and while it is a decent treatment, it is not feasible in the long run for consistent reference because of the effects of radiation and the growing resistance that cancer cells develop. As a result of cancer cells having mutations that can result in “hidden” receptors, making them undiscoverable by the body's T cells, immunotherapy has emerged as a new approach to cancer treatments. Adoptive cell therapies using chimeric antigen receptor (CAR) T cells, more specifically, have shown promise due to their ability to incorporate the receptors and antibodies necessary to discover the cancer cells despite mutated patterns. Umbilical Cord Blood (UCB) T cells are a new, up and coming technology that are obtained through derivation from umbilical cord blood. In this thesis, UCB T cells are combined with 3 variable expansion systems and cultured with and without transduction to determine proliferation rate, phenotypic qualities, and CAR expression to determine the capabilities of their usage as an allogeneic adoptive cell therapy.
(Georgia Institute of Technology, 2021-12)
Frey, David A.
Approximately 6 million bone fractures are reported annually within the US, 10% of which may experience complications, such as nonunion (permanent failure to heal) or delayed healing. These complications often result in prolonged hospital visits and/or increased financial burden on the patients. To expedite bone healing, researchers have explored implanting biomaterial scaffolds for critical breaks, delivery of bone morphogenic proteins (BMPs), and improving vascularization of damaged regions. Recent studies, however, have shed light on the role of inflammatory cells in the bone repair process. Furthermore, studies have shown scenarios involving chronic inflammation, such as bone fractures, stimulate the proliferation and activation of myeloid-derived immunosuppressor cells (MDSCs). MDSCs are a heterogeneous population of immature myeloid cells that are categorized into two subsets: Ly6G(+) Ly6C(low) granulocytic (G-MDSC) and Ly6G(-) Ly6C(high) monocytic cells (M-MDSC). Differences between these two groups primarily lies in their respectively low/high production of nitric oxide (NO) and reactive oxidative species (ROS). Both subsets have been found to inhibit inflammatory cell activity during the bone repair process, indicating that these cells may be a potential target for immunomodulatory strategies. One such strategy, synthetic nanoparticle antibodies (SNAb), was previously developed in our lab to specifically deplete MDSCs while restoring effector cell activity. Here we explore the optimization of SNAb fabrication, and the effect of SNAbs on the presence of certain cell types in musculoskeletal tissue.
(Georgia Institute of Technology, 2021-05)
Phang, Katelynn
Although many studies have been done on antibodies and vaccines, little is known about the transfection methods of nanoparticles capable of carrying antigens into cells to create effective mRNA vaccines. Although mRNA vaccines, particularly lipid nanoparticle based COVID vaccines, have been recognized for their rapid development potential, high potency, and lower production costs, there are still many considerations that must be made such as efficacy, side effect incidence, and persistence. This study seeks to elucidate the potential effectiveness of polymer nanoparticles, particularly chitosan nanoparticles, for mRNA vaccine use to improve upon current standard lipid nanoparticles. The results from uptake, ROS, and RNS experiments indicate that chitosan, a polymer nanoparticle, exhibits desired uptake but not mRNA expression. As such, further studies such as gene knockouts will need to be done to clarify exactly why the mRNA expression does not reach desired levels.