Engineered cells and methods of use

Abstract

Provided herein are engineered cells, comprising: a chemical or biological moiety covalently bound to a cell surface glycan, wherein the chemical or biological moiety is selected from the group consisting of small molecule, polynucleotide, polypeptide, and antibody. Also provided are compositions comprising these engineered cells and methods of making and using the same.

What is claimed is: 
     
         1 . An engineered cell, comprising an antibody covalently bound to a N-acetyllactosamine (LacNAc) glycan on the surface of a cell via a sialic acid linkage. 
     
     
         2 . The engineered cell of  claim 1 , wherein formation of the sialic linkage between the antibody and the cell surface glycan is catalyzed by a sialyltransferase. 
     
     
         3 . The engineered cell of  claim 1 , wherein the cell is a primary human T cell, a natural killer (NK) cell, a CD4+ cell, or a primary CD8+ OT-1 T cells. 
     
     
         4 . The engineered cell of  claim 3 , wherein the NK cell is NK-92MI cell. 
     
     
         5 . The engineered cell of  claim 1 , wherein the antibody is a single chain variable fragment (scFv), fragment antigen binding (Fab) fragment, or a full length antibody. 
     
     
         6 . The engineered cell of  claim 1 , wherein the antibody is an immunoglobulin G (IgG) antibody. 
     
     
         7 . The engineered cell of  claim 1 , wherein the antibody is Trastuzumab. 
     
     
         8 . The engineered cell of  claim 1 , wherein the cell is a chimeric antigen receptor (CAR)-T cell. 
     
     
         9 . The engineered cell of  claim 8 , comprising a genetically modified T-cell with the cell surface LacNAc covalently bound to a sialic acid bearing a new motif. 
     
     
         10 . An engineered cell, comprising:
 a chemical or biological moiety covalently bound to a cell surface glycan present on the surface of the cell,   wherein the chemical or biological moiety is selected from the group consisting of small molecule, polynucleotide, polypeptide, and antibody.   
     
     
         11 . The engineered cell of  claim 10 , wherein the engineered cell is an immune cell. 
     
     
         12 . The engineered cell of  claim 11 , wherein the immune cell is a T-cell or a natural killer (NK) cell. 
     
     
         13 . The engineered cell of  claim 12 , wherein the T cell is a CD8+ or a CD4+ T cell. 
     
     
         14 . The engineered cell of  claim 11 , wherein the immune cell is a Dendritic Cell (DC). 
     
     
         15 . The engineered cell of  claim 10 , wherein the small molecule is a small drug molecule or a pharmaceutically acceptable salt or a co-crystal thereof. 
     
     
         16 . The engineered cell of  claim 10 , wherein the chemical or biological moiety is a biotin probe, a fluorescent probe, a biorthogonal reaction handle, and/or a dye labeled single strand DNA. 
     
     
         17 . A method of making an engineered cell, comprising:
 generating CMP-sialic acid conjugated with an antibody (CS-IgG) by reacting an antibody bearing a TCO moiety with CS-Az-Tz or CS-Poc-Tz; and   making the engineered cell by incubating a naturally occurring cell with a composition comprising (a) CS-IgG and (b) a sialyltransferase.   
     
     
         18 . The method of  claim 17 , wherein the sialyltransferase is selected from the group consisting of ST6Gal1, Pasteurella multocida α(2,3) sialyltransferase M144D mutant (Pm2,3 ST-M144D), and Photobacterium damsel a(2,6) sialyltransferase (Pd2,6ST). 
     
     
         19 . A method of treating or inhibiting the growth of a cancer in a subject, comprising administering to the subject a therapeutically effective dosage of the engineered cell, wherein the engineered cell of  claim 1 , thereby treating or inhibiting the growth of the cancer in the subject. 
     
     
         20 . The method of  claim 19 , wherein the cell is NK-92MI, and the antibody is Trastuzumab.