ERI: Bioengineering Synthetic Antigen-Presenting Cells for Controlled Immune Modulation

A dendritic cell is an immune cell that captures foreign particles, or antigens, in the body and presents them to other immune cells to begin an immune response. Dendritic cells are important because they can initiate the body’s defense against infections and prevent autoimmunity, which is when the body mistakenly attacks its own healthy organs and tissues. Dendritic cells could be a target for new therapeutics, but it is very difficult to accurately control them. The goal of this project is to produce synthetic antigen-presenting cells (SAPCs) that recreate the activities of natural dendritic cells. Using new tools in nanotechnology and bioengineering, the project will develop SAPCs that can present antigens to other immune cells to improve the immune response to the antigens. This work will provide new knowledge on how the size of SAPCs affects their function and will explore engineering strategies to develop size-changing SAPCs for optimal immune stimulation. The project will also have significant educational and societal influence. The research activities will be incorporated into existing summer programs at the Joint School of Nanoscience and Nanoengineering that will provide direct research experience to high school and undergraduate students and provide graduate students with excellent opportunities to develop their research skills and contribute to groundbreaking discoveries.

Dendritic cells play a critical role in balancing immune activation and suppression, thereby making them valuable candidates for adoptive cell therapy in various medical conditions. However, their clinical use is limited by their sensitivity to the changes in the microenvironment and their association with adverse events. This research project will address these challenges by developing synthetic antigen-presenting cells (SAPCs) that precisely control the immune response. SAPCs are bioengineered constructs that retain only the essential functional molecules necessary for effective T cell priming and activation. The proposed work aims to elucidate how the size of SAPCs influences their function, with the goal to develop and evaluate size-tunable SAPCs that enhance T cell activation and adaptive immune response for immunotherapeutic applications. The approach integrates biological membrane extrusion with bioorthogonal click chemistry to fabricate SAPC constructs with adaptive size control, which enables a systematic investigation of how physical properties affect immune response. The research is organized into three primary aims. Aim 1 will focus on elucidating the impact of SAPC sizes on T cell activation, aim 2 is designed to develop size-changing SAPCs for enhanced immune stimulation following efficient tissue penetration, and aim 3 will validate the T cell stimulation efficacy of both static-size and size-changing SAPCs. This work is significant in advancing the fundamental understanding of how physical properties regulate immune responses and in driving engineering innovations toward scalable, size-tunable immunotherapeutic platforms.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

Award Number: 2501889
Principal Investigator: Kerui Wu
Funds Obligated: $199,998
State: NC