Abstract
Immunotherapies, such as chimeric antigen receptor (CAR) T-cells and immune checkpoint blockades (ICB), have transformed hematologic malignancy treatment options but have not had similar impacts on solid tumors (1, 2). These treatments are limited to finite target antigens or require a patient’s own primed antitumor T-cell population, respectively (3, 4). To overcome these limitations, we engineered conventional type 1 dendritic cells (DCs) with an antitumor binding, toll-like receptor 4 (TLR4) signaling CAR to harness the DCs ability to cross prime a broad repertoire of antitumor CD8 T-cells. In vitro, the CAR-DC lead to increased tumor uptake, DC maturation, and cross-priming of tumor-reactive CD8 T-cells. CAR-DCs lead to complete rejection of an orthotopic solid tumor model with heterogenous CAR target expression. The antitumor T-cell population from CAR-DC treated mice showed an improved T-cell response against more than one endogenous tumor antigen, increased activation, and more robust persistence of tumor-reactive clones.
Committee Chair
Carl DeSelm
Committee Members
Kenneth Murphy; Nathan Singh; Robert Schreiber; Todd Fehniger
Degree
Doctor of Philosophy (PhD)
Author's Department
Biology & Biomedical Sciences (Immunology)
Document Type
Dissertation
Date of Award
12-17-2025
Language
English (en)
DOI
https://doi.org/10.7936/gwt7-7d25
Author's ORCID
0000-0001-5006-9020
Recommended Citation
Namen, Shelby, "Engineering Dendritic Cells with a Chimeric Antigen Receptor for Enhanced Antitumor Function" (2025). Arts & Sciences Theses and Dissertations. 3686.
The definitive version is available at https://doi.org/10.7936/gwt7-7d25