Devices, systems and methods for cell modification

Abstract

A method of modifying cells includes removing fluid including cells from a patient, contacting the removed fluid from the patient with at least one surface upon which at least one agent to interact at least one cell receptor is immobilized to modify cells in the fluid, and returning the fluid to the patient. The agent can, for example, be immobilized via covalent bonding or ionic bonding to the at least one surface. The fluid can, for example, be blood or a blood fraction. The agent can, for example, be an agonist, an antagonist or an inverse agonist.

1 . A method of modifying cells comprising: removing fluid including cells from a patient, contacting the removed fluid from the patient with at least one surface upon which at least one agent to interact at least one cell receptor is immobilized to modify cells in the fluid, and returning the fluid to the patient. 
     
     
         2 . The method of  claim 1  wherein the fluid is blood or a blood fraction. 
     
     
         3 . The method of  claim 2  wherein the agent is an agonist, an antagonist or an inverse agonist. 
     
     
         4 . The method of  claim 2  wherein the agent comprises a protein or a fragment of a protein. 
     
     
         5 . The method of  claim 2  wherein the agent comprises a cytokine. 
     
     
         6 . The method of  claim 5  wherein the cytokine is a chemokine. 
     
     
         7 . The method of  claim 6  wherein the agent is an interleukin. 
     
     
         8 . The method of  claim 6  wherein the agent is IL-8 (interleukin 8). 
     
     
         9 . The method of  claim 2  in which the blood or the blood fraction is passed in a continuous loop from a blood vessel of the patient to contact the at least one surface and back to a blood vessel of the patient. 
     
     
         10 . The method of  claim 2  wherein the blood or the blood fraction is passed continuously for at least a period of time from a blood vessel of the patient to contact the at least one surface and back to the blood vessel. 
     
     
         11 . The method of  claim 2  wherein the blood or the blood fraction is passed discontinuously from a blood vessel of the patient to contact the at least one surface and back to the blood vessel. 
     
     
         12 . The method of  claim 2  wherein cells are modified to treat sepsis. 
     
     
         13 . The method of  claim 2  wherein blood or the blood fraction is contacted with the at least one surface in an extracorporeal device comprising the at least one surface. 
     
     
         14 . The method of  claim 2  wherein the extracorporeal device comprises a plurality of surfaces upon which at least one agent to interact with at least one cell receptor is immobilized. 
     
     
         15 . The method of  claim 14  wherein the plurality of surfaces comprise a plurality of hollow fibers. 
     
     
         16 . The method of  claim 14  wherein the plurality of surfaces comprise a plurality of beads. 
     
     
         17 . The method of  claim 2  wherein the agent is a ligand selected from the group of IL-1, IL-4, IL-6, IL-8, IL-10, IL-18, IL-33, TNF, FAS, MIF, Flt3, a ligand form the Bcl-2 family of ligands, an L-selectin, a P-selectin, ICAM-1 or an antibody. 
     
     
         18 . The method of  claim 2  wherein the agent is immobilized via covalent bonding or ionic bonding to the at least one surface. 
     
     
         19 . The method of  claim 2  wherein the period of contact for cells targeted for modification is extended. 
     
     
         20 . The method of  claim 19  wherein the period of contact for cells targeted for modification is extended by the immobilization of an adhesion agent on the at least one surface, by at least one physiological characteristic of the at least one surface, or by a geometry of a volume through which the fluid containing cells flows. 
     
     
         21 . The method of  claim 2  wherein cells are modified in treatment of sepsis, treatment of inflammatory disease, treatment of cancer, immune system regulation, or treatment of cardiovascular disease. 
     
     
         22 . The method of  claim 2  wherein white blood cells are modified. 
     
     
         23 . The method of  claim 2  wherein neutrophils are modified. 
     
     
         24 . An extracorporeal device comprising a vessel, an inlet adapted to pass fluid including cells removed from a patient into the vessel, at least one surface within the vessel upon which at least one agent to interact with at least one cell receptor is immobilized, and an outlet adapted to return the fluid from the vessel to the patient. 
     
     
         25 . The device of  claim 24  comprising a plurality of surfaces upon which at least one agent to interact with at least one cell receptor is immobilized. 
     
     
         26 . The device of  claim 25  wherein the plurality of surfaces comprise a plurality of hollow fibers. 
     
     
         27 . The device of  claim 25  wherein the plurality of surfaces comprise a plurality of beads. 
     
     
         28 . The device of  claim 24  wherein the agent is an agonist, an antagonist or an inverse agonist. 
     
     
         29 . The device of  claim 24  wherein the agent comprises a protein or a fragment of a protein. 
     
     
         30 . The device of  claim 24  wherein the agent comprises a cytokine. 
     
     
         31 . The device of  claim 29  wherein the cytokine is a chemokine. 
     
     
         32 . The device of  claim 31  wherein the agent is an interleukin. 
     
     
         33 . The device of  claim 31  wherein the agent is IL-8 (interleukin 8). 
     
     
         34 . The device of  claim 24  in which the fluid is passed in a continuous loop from a blood vessel of the patient to contact the at least one surface and back to a blood vessel of the patient. 
     
     
         35 . The device of  claim 24  wherein the fluid is passed continuously for at least a period of time from a blood vessel of the patient to contact the at least one surface and back to the blood vessel. 
     
     
         36 . The device of  claim 24  wherein the fluid is passed discontinuously from a blood vessel of the patient to contact the at least one surface and back to the blood vessel. 
     
     
         37 . The device of  claim 24  wherein the agent is a ligand selected from the group of IL-1, IL-4, IL-6, IL-8, IL-10, IL-18, IL-33, TNF, FAS, MIF, Flt3, a ligand form the Bcl-2 family of ligands, an L-selectin, a P-selectin, ICAM-1 or an antibody. 
     
     
         38 . The device of  claim 24  wherein the agent is immobilized via covalent bonding or ionic bonding to the at least one surface. 
     
     
         39 . The device of  claim 24  wherein the residence time for cells targeted for modification within the devices is extended. 
     
     
         40 . The device of  claim 39  wherein the residence time for cells targeted for modification is extended by the immobilization of an adhesion agent on the at least one surface, by at least one physiological characteristic of the at least one surface, or by a geometry of a volume through which the fluid containing cells flows. 
     
     
         41 . A system for modifying cells comprising:
 a first conduit adapted to be placed in fluid connection with a patient,   an extracorporeal device comprising a vessel, an inlet in fluid connection with the first conduit, at least one surface within the vessel upon which at least one agent to interact at least one cell receptor is immobilized, and an outlet;   a second conduit in fluid connection with the outlet and adapted to be placed in fluid connection with the patient; and   at least one pump system to circulate fluid from the patient through the system.   
     
     
         42 . The system of  claim 41  wherein the extracorporeal device comprises a plurality of surfaces upon which at least one agent to interact with at least one cell receptor is immobilized. 
     
     
         43 . The system of  claim 42  wherein the plurality of surfaces comprise a plurality of hollow fibers. 
     
     
         44 . The system of  claim 42  wherein the plurality of surfaces comprise a plurality of beads.