DNA-Edited Ligand Positioning on Red Blood Cells to Enable Optimized T Cell Activation for Adoptive Immunotherapy
Lele Sun,1 Fengyun Shen,1 Jun Xu,1 Xiao Han,1 Chunhai Fan2 and Zhuang Liu1,*
1Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Lab Carbon Based Functional Materials and Devices, Soochow University, Suzhou, 215123, Jiangsu (China)
2School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, 201240 (China)
Artificial antigen presenting cells (aAPCs) with surface-anchored T cell activating ligands hold great potential in adoptive immunotherapy. However, it remains challenging to precisely control the ligand positioning on those platforms using conventional bioconjugation chemistry. Utilizing DNA-assisted bottom-up self-assembly, we were able to precisely control both lateral and vertical distributions of T cell activation ligands on red blood cells (RBCs). The clustered lateral positioning of the peptide-major histocompatibility complex (pMHC) on RBCs with a short vertical distance to the cell membrane is favorable for more effective T cell activation, likely owing to their better mimicry of natural APCs. Such optimized RBC-based artificial APCs can stimulate T cell proliferation in vivo and effectively inhibit tumor growth with adoptive immunotherapy. DNA technology is thus a unique tool to precisely engineer the cell membrane interface and tune cell–cell interactions, which is promising for applications such as immunotherapy.