ASU Electronic Theses and Dissertations
This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
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- All Subjects: cancer immunotherapy
- All Subjects: Product Allocation
Description
Peptide-based vaccines represent a promising strategy to develop personalized treatments for cancer immunotherapy. Despite their specificity and low cost of production, these vaccines have had minimal success in clinical studies due to their lack of immunogenicity, creating a need for more effective vaccine designs. Adjuvants can be incorporated to enhance their immunogenicity by promoting dendritic cell activation and antigen cross-presentation. Due to their favorable size and ability to incorporate peptides and adjuvants, nanoparticles represent an advantageous platform for designing peptide vaccines. One prime example is RNA origami (RNA-OG) nanostructures, which are nucleic acid nanostructures programmed to assemble into uniform shapes and sizes. These stable nanostructures can rationally incorporate small molecules giving them a wide array of functions. Furthermore, RNA-OG itself can function as an adjuvant to stimulate innate immune cells. In the following study, self-adjuvanted RNA-OG was employed as a vaccine assembly platform, incorporating tumor peptides onto the nanostructure to design RNA-OG-peptide nanovaccines for cancer immunotherapy. RNA-OG-peptide was found to induce dendritic cell activation and antigen cross-presentation, which mobilized tumor-specific cytotoxic T cells to elicit protective anti-tumor immunity in tumor-bearing mice. These findings demonstrate the therapeutic potential of RNA-OG as a stable, carrier-free nanovaccine platform. In an attempt to further enhance the efficacy by optimizing the amount of peptides assembled, RNA-OG was complexed with polylysine-linked peptides, a simple strategy that allowed peptide amounts to be varied. Interestingly, increasing the peptide load led to decreased vaccine efficacy, which was correlated with an ineffective CD8+ T cell response. On the other hand, the vaccine efficacy was improved by decreasing the amount of peptide loaded onto RNA-OG, which may have attributed to greater complex stability compared to the high peptide load. These results highlight a simple strategy that can be used to optimize vaccine efficacy by altering the load of assembled peptides. These studies advance our understanding of RNA-OG as a peptide vaccine platform and provide various strategies to improve the design of peptide vaccines for translation into cancer immunotherapy.
ContributorsYip, Theresa (Author) / Chang, Yung (Thesis advisor) / Borges Florsheim, Esther (Committee member) / Lake, Douglas (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2024
Description
To maintain long term success, a manufacturing company should be managed and operated under the guidance of properly designed capacity, production and logistics plans that are formulated in coordination with its manufacturing footprint, so that its managerial goals on both strategic and tactical levels can be fulfilled. In particular, sufficient flexibility and efficiency should be ensured so that future customer demand can be met at a profit. This dissertation is motivated by an automobile manufacturer's mid-term and long-term decision problems, but applies to any multi-plant, multi-product manufacturer with evolving product portfolios and significant fixed and variable production costs. Via introducing the concepts of effective capacity and product-specific flexibility, two mixed integer programming (MIP) models are proposed to help manufacturers shape their mid-term capacity plans and long-term product allocation plans. With fixed tooling flexibility, production and logistics considerations are integrated into a mid-term capacity planning model to develop well-informed and balanced tactical plans, which utilize various capacity adjustment options to coordinate production, inventory, and shipping schedules throughout the planning horizon so that overall operational and capacity adjustment costs are minimized. For long-term product allocation planning, strategic tooling configuration plans that empower the production of multi-generation products at minimal configuration and operational costs are established for all plants throughout the planning horizon considering product-specific commonality and compatibility. New product introductions and demand uncertainty over the planning horizon are incorporated. As a result, potential production sites for each product and corresponding process flexibility are determined. An efficient heuristic method is developed and shown to perform well in solution quality and computational requirements.
ContributorsYao, Xufeng (Author) / Askin, Ronald (Thesis advisor) / Sefair, Jorge (Thesis advisor) / Escobedo, Adolfo (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2021