Reversible re-programing of cell-cell interactions.
The ability to engineer and re-program the surfaces of cells would provide an enabling synthetic biological method for the design of cell- and tissue-based therapies. A new cell surface-engineering strategy is described that uses lipid-chemically self-assembled nanorings (lipid-CSANs) that can be used for the stable and reversible modification of any cell surface with a molecular reporter or targeting ligand. In the presence of a non-toxic FDA-approved drug, the nanorings were quickly disassembled and the cell-cell interactions reversed. Similar to T-cells genetically engineered to express chimeric antigen receptors (CARS), when activated peripheral blood mononuclear cells (PBMCs) were functionalized with the anti-EpCAM-lipid-CSANs, they were shown to selectively kill antigen-positive cancer cells. Taken together, these results demonstrate that lipid-CSANs have the potential to be a rapid, stable, and general method for the reversible engineering of cell surfaces and cell-cell interactions.
Department of Medicinal Chemistry, University of Minnesota, 308 Harvard Street SE, Minneapolis, MN 55455 (USA).
Kari
K
Gabrielse
Amit
A
Gangar
Nigam
N
Kumar
Jae Chul
JC
Lee
Adrian
A
Fegan
Jing Jing
JJ
Shen
Qing
Q
Li
Daniel
D
Vallera
Carston R
CR
Wagner
D002450:Cell Communication; D065150:Cellular Reprogramming; D005434:Flow Cytometry; D006801:Humans; D061986:MCF-7 Cells; D049329:Nanostructures
cell-cell interactions; chimeric antigen receptors; nanoparticles; oligomerization; self-assembly