DNA-Edited Ligand Positioning on Red Blood Cells to Enable Optimized T Cell Activation for Adoptive Immunotherapy.
Lele SunFengyun ShenJun XuXiao HanChunhai FanZhuang LiuPublished in: Angewandte Chemie (International ed. in English) (2020)
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.
Keyphrases
- red blood cell
- cell therapy
- circulating tumor
- cell free
- single molecule
- cell proliferation
- stem cells
- single cell
- mesenchymal stem cells
- induced apoptosis
- crispr cas
- minimally invasive
- signaling pathway
- nucleic acid
- cell cycle
- case report
- bone marrow
- circulating tumor cells
- endoplasmic reticulum stress
- pi k akt
- human health
- drug discovery