Augmentation of Cell Therapy Efficacy Including Treatment With Alpha 1,3 Fucosyltransferase

Abstract

Disclosed are methods, compositions of matter, and kits useful for augmentation of cells through modification of cellular membrane properties following ex vivo treatment.

What is claimed is: 
     
         1 . A method of enhancing homing and engraftment of one or more T cells, the method comprising the step of:
 contacting a T cell population with α1,3-fucosyltransferase VI ex vivo to fucosylate at least one surface molecule on the T cell(s) to enhance selectin mediated binding thereof.   
     
     
         2 . The method of  claim 1 , wherein the T cell population is further defined as an ex vivo expanded T cell population. 
     
     
         3 . The method of  claim 1 , wherein the T cell population is further defined as a heterogeneous population of T cells. 
     
     
         4 . The method of  claim 1 , wherein the T cell population comprises Regulatory T cells. 
     
     
         5 . The method of  claim 1 , further comprising the steps of:
 contacting the T cell population with a fucose carrier; and   combining said fucosylated T cells with a pharmaceutically-acceptable carrier to provide a composition capable of administration via a route selected from a group comprising intravenously, intraarterially, intramuscularly, subcutaneously, transdermally, intratracheally, intraperitoneally, intravitreally, and combinations thereof.   
     
     
         6 . The method of  claim 5 , wherein the fucose carrier is mixed with alpha 1,3-fucosyltransferase VI prior to contacting said mixture with the T cell population, and wherein said fucose carrier is guanosine diphosphate fucose. 
     
     
         7 . A method of enhancing homing and engraftment of one or more T cells, the method comprising the step of:
 contacting a T cell population with α1,3-fucosyltransferase VII ex vivo to fucosylate at least one surface molecule on the T cell(s) to enhance selectin mediated binding thereof.   
     
     
         8 . The method of  claim 7 , wherein the T cell population is further defined as an ex vivo expanded T cell population. 
     
     
         9 . The method of  claim 7 , wherein the T cell population is further defined as a heterogeneous population of T cells. 
     
     
         10 . The method of  claim 7 , wherein the T cell population comprises Cytotoxic T cells. 
     
     
         11 . The method of  claim 7 , further comprising the steps of:
 contacting the T cell population with a fucose carrier; and   combining said fucosylated T cells with a pharmaceutically-acceptable carrier to provide a composition capable of administration via a route selected from a group comprising intravenously, intraarterially, intramuscularly, subcutaneously, transdermally, intratracheally, intraperitoneally, intravitreally, and combinations thereof.   
     
     
         12 . The method of  claim 11 , wherein the fucose carrier is mixed with alpha 1,3-fucosyltransferase VI prior to contacting said mixture with the T cell population, and wherein said fucose carrier is guanosine diphosphate fucose. 
     
     
         13 . A method of enhancing homing and engraftment of a T cell population, the method comprising the step of:
 administering an ex vivo expanded population of fucosylated T cells to a patient in need thereof, the population of cells being fucosylated by contact with α1,3-fucosyltransferase VI and/or α1,3-fucosyltransferase VII that fucosylated at least one surface molecule on the T cells to enhance selectin mediated binding thereof.   
     
     
         14 . The method of  claim 13 , wherein the population of fucosylated T cells is further defined as a heterogeneous population of fucosylated T cells. 
     
     
         15 . The method of  claim 13 , wherein the population of fucosylated T cells comprises Regulatory T cells that have been fucosylated by contact with α1,3-fucosyltransferase VI. 
     
     
         16 . The method of  claim 13 , wherein the population of fucosylated T cells comprises Cytotoxic T cells that have been fucosylated by contact with α1,3-fucosyltransferase VII. 
     
     
         17 . The method of  claim 13 , wherein the patient suffers from at least one condition selected from the group comprising a myelodysplastic syndrome, a stem cell disorder, a myeloproliferative disorder, a lymphoproliferative disorder, a phagocyte disorder, a histiocytic disorder, a liposomal storage disease, a congenital immune system disorder, an inherited erythrocyte abnormality, an inherited platelet abnormality, a plasma cell disorder, a tumor, an autoimmune disease, and combinations thereof. 
     
     
         18 . The method of  claim 13 , wherein the patient in need of treatment with the modified cell population suffers from at least one condition selected from the group comprising peripheral arterial diseases, ischemic limb injury, diabetes, heart disease, liver disease, bone disease, muscular dystrophy, Alzheimer's disease, ALS, multiple sclerosis, Parkinson's disease, spinal cord injury, stroke, head trauma, infertility, and combinations thereof. 
     
     
         19 . The method of  claim 13 , wherein the population of fucosylated T cells is administered via a route selected from a group comprising intravenously, intraarterially, intramuscularly, subcutaneously, transdermally, intratracheally, intraperitoneally, intravitreally, and combinations thereof. 
     
     
         20 . The method of  claim 13 , wherein the population of fucosylated T cells is administered to a site of injury or proximal thereto.