Engineering dendritic cells for enhanced cancer immunotherapy
Han, Joonsu
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Permalink
https://hdl.handle.net/2142/127387
Description
Title
Engineering dendritic cells for enhanced cancer immunotherapy
Author(s)
Han, Joonsu
Issue Date
2024-12-05
Director of Research (if dissertation) or Advisor (if thesis)
Wang, Hua
Doctoral Committee Chair(s)
Wang, Hua
Committee Member(s)
Leal, Cecilia
Chen, Qian
Harley, Brenden
Nie, Shuming
Department of Study
Materials Science & Engineerng
Discipline
Materials Science & Engr
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Cancer Immunotherapy
Biomaterials
Dendritic cell
DC engineering
Abstract
Therapeutic cancer vaccines consist of two key components: a tumor antigen and an adjuvant. The tumor antigen is presented by dendritic cells (DCs), while the adjuvant activates DCs to prime T cells. Currently, there are only five FDA-approved adjuvants, offering limited options. Tumor antigens, however, can be sourced through various methods, such as extracellular vesicles, which takes a few days, or peptide sequencing, which may take several weeks. More advanced methods like tumor antigen-encoding mRNA synthesis offer greater specificity but require more time, often six weeks or longer. This trade-off between the speed of vaccine production and specificity poses a challenge, as many cancer patients cannot afford delays in treatment. Thus, it is crucial to develop various therapeutic cancer vaccine platforms that enable both timely and effective treatment across a broad range of cancer cases.
In response to this need for innovative and versatile cancer vaccine platforms, my Ph.D. research focuses on developing novel strategies for engineering DCs with various tumor antigen sources to create potent cancer immunotherapies. The upcoming chapters are structured to achieve several key objectives. Chapter 1 investigates the use of cationic α-helical polypeptides as delivery vehicles for tumor antigen-encoding mRNAs, aiming to activate DCs during the delivery process. Chapter 2 examines how unnatural sugars can modify the biophysical properties of dendritic cell membranes, leading to DC activation and enhancing their capacity to process and present tumor antigen peptides, thereby contributing to the development of improved DC vaccines. Chapter 3 details the development of a bioadhesive macroporous hydrogel designed to attract and reprogram DCs in situ using tumor extracellular vesicles, enabling them to effectively elicit cytotoxic T lymphocyte (CTL) responses against cancer. Together, these efforts to develop cancer vaccine platforms through various strategies for engineering DCs offer comprehensive, potent, and safe cancer immunotherapies that we hope will ultimately translate into clinical applications to benefit cancer patients.
Beyond DC engineering for developing cancer vaccines, I have also explored material-tissue interactions. Chapter 4 discovers a novel bio-adhesion chemistry that enables double crosslinking between materials and tissue surfaces, broadening design options for bioadhesives to ensure stable adhesion. Lastly, chapter 5 demonstrates an adaptive surgical adhesive inspired by the protective mechanisms of plant seed coatings, which responds to anastomotic leaks, presenting a promising sealant for gastrointestinal surgeries.
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