Engineering extracellular vesicles and immune cell homing materials for next generation cancer immunotherapy

My Ph.D. research focuses on developing innovative technologies to enable precise and effective modulation of dendritic cells (DCs), to advance cancer immunotherapies that elicit durable cytotoxic T lymphocyte (CTL) responses and robust antitumor efficacy. My work spans two key material platforms: nanosized extracellular vesicles (EVs) and macroscale immune cell-homing biomaterials. For EVs, I developed a novel metabolic tagging technology that installs chemical tags (e.g., azido groups) onto the surface of cell-secreted exosomes, enabling the conjugation of immunomodulatory agents through efficient click chemistry. This approach allows for the functionalization and modulation of EVs to enhance their processing by DCs, leading to improved T-cell priming and antitumor activity. For immune cell-homing biomaterials, I designed a prototype cancer immunotherapy platform using DC-homing macroporous hydrogels with tunable pore size and mechanical properties. Together, these technologies aim to provide tailored solutions for enhancing immune responses and overcoming challenges in cancer immunotherapy. Chapter I introduces the foundational concepts of this research and outlines the current challenges and limitations in the field of cancer immunotherapy. Chapter II explores metabolic tagging and targeting strategies for extracellular vesicles (EVs), focusing on the development of next-generation EV vaccines. By conjugating adjuvants (e.g., CpG) to EVs, we demonstrate the induction of robust cytotoxic T lymphocyte (CTL) responses and enhanced antitumor efficacy. Building on this, Chapter III investigates the potential of antibody-conjugated tumor EVs (e.g., anti-DEC205) as therapeutic cancer vaccines, improving the targeting efficiency and activation of dendritic cells (DCs). Chapter IV extends this work by leveraging chemically tagged exosomes to develop exosome-based hydrogels, which function as potent in situ depot vaccines for sustained immune modulation. In parallel, Chapter V delves into the rational design of immune cell-homing macroporous materials, which preferentially recruit specific immune cells (e.g., DCs) to the material site in vivo, serving as a prototype for cancer immunotherapy. Finally, Chapter VI highlights the ability of these immune cell-homing materials to recruit and modulate T cells in vivo, supporting the development of advanced T cell therapies. Together, these chapters present a comprehensive approach to advancing cancer immunotherapy through innovative biomaterial and EV-based strategies.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Materials Science & Engr

Grantor

University of Illinois Urbana-Champaign

Year dc:date

2025

Author dc:creator

• Bhatta, Rimsha

Contributors dc:contributor

• Wang, Hua
• Leal, Cecilia
• Chen, Qian
• Bhargava, Rohit
• Nelson, Erik R.

• Cancer Immunotherapy
• Biomaterial
• Hydrogel
• Extracellular Vesicle
• Dendritic Cell

Statement dc:rights

• Copyright 2025 Rimsha Bhatta

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/129492

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F129492