Engineering dendritic cells for enhanced cancer immunotherapy

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Materials Science & Engr

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2024

Author dc:creator

• Han, Joonsu

Contributors dc:contributor

• Wang, Hua
• Leal, Cecilia
• Chen, Qian
• Harley, Brenden
• Nie, Shuming

• Cancer Immunotherapy
• Biomaterials
• Dendritic Cell
• Dc Engineering

Statement dc:rights

• Copyright 2024 Joonsu Han

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/127387

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F127387