Cell Expansion

Patent metadata

Field	Value
Publication number	US-2016333314-A1
Application number	US-201615153396-A
Country	US
Kind code	A1
Filing date	May 12, 2016
Priority date	May 13, 2015
Publication date	Nov 17, 2016
Grant date	—

Abstract

Embodiments are described that relate to methods and systems for growing cells in a hollow fiber bioreactor. In embodiments, the cells may be exposed to an activator for activating expansion of the cells. The cells may in embodiments include T cells, and the activator may be in different forms, including, for example, antigen presenting cells or beads functionalized with antibodies.

First claim

What is claimed is:

1 . A method of expanding cells, the method comprising:
introducing a first plurality of cells comprising leukocytes into a hollow fiber bioreactor, wherein the hollow fiber bioreactor comprises a plurality of hollow fibers; exposing the first plurality of cells to an activator to activate expansion of the cells in the hollow fiber bioreactor; expanding at least a portion of the first plurality of cells in the plurality of hollow fibers of the bioreactor to generate a second plurality of expanded cells; and removing the second plurality of expanded cells from the bioreactor.

2 . The method of claim 1 , wherein the portion of the first plurality of cells comprises T cells.

3 . The method of claim 2 , wherein the first plurality of cells is generated using a leukapheresis procedure.

4 . The method of claim 3 , wherein the first plurality of cells are added to the hollow fiber bioreactor without additional purification.

5 . The method of claim 4 , wherein the first plurality of cells comprise red blood cells.

6 . The method of claim 5 , wherein the first plurality of cells comprise platelets.

7 . The method of claim 6 , wherein the first plurality of cells comprise granulocytes.

8 . The method of claim 7 , wherein the exposing comprises exposing the first plurality of cells to beads that comprise the activator on their surface.

9 . The method of claim 7 , wherein the exposing comprises exposing the first plurality of cells to dendritic cells that comprise the activator.

10 . The method of claim 9 , wherein the activator comprises one or more antigens.

11 . The method of claim 8 , wherein the activator comprises one or more antibodies selected from the group consisting of anti-CD2, anti-CD3, anti-CD28, and combinations thereof.

12 . The method of claim 1 , wherein the steps are performed in a closed system.

13 . The method of claim 11 , wherein the expanding comprises circulating media in the hollow fiber bioreactor.

14 . The method of claim 13 , wherein the media comprises one or more of, interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 7 (IL-7), interleukin 15 (IL-15), and combinations thereof.

15 . A cell expansion system for expanding cells, the system comprising:
a hollow fiber bioreactor comprising a first fluid flow path having at least opposing ends, wherein a first opposing end of the first fluid flow path is fluidly associated with a first port of the hollow fiber bioreactor, and a second end of the first fluid flow path is fluidly associated with a second port of the hollow fiber bioreactor, wherein the first fluid flow path comprises an intracapillary portion of the hollow fiber bioreactor;
a fluid inlet path fluidly associated with the first fluid flow path, wherein a plurality of cells are introduced into the first fluid flow path through the first fluid inlet path;
a first pump for circulating fluid in the first fluid flow path;
a processor for executing processor executable instructions; a memory for storing instructions that when executed by the processor perform a method comprising:
introducing a first fluid comprising a first plurality of cells comprising leukocytes into the intracapillary portion of the hollow fiber bioreactor;
exposing the first plurality of cells to a first activator in the intracapillary portion to activate expansion of the cells in the hollow fiber bioreactor;
introducing a second fluid comprising media into the intracapillary portion to expand at least a portion of the first plurality of cells and generate a second plurality of expanded cells; and
removing the second plurality of expanded cells from the bioreactor.

16 . The system of claim 15 , wherein the system is a closed system.

17 . The system of claim 16 , wherein the second plurality of expanded cells comprise T cells.

18 . The system of claim 14 , wherein the first fluid comprises beads that comprise the first activator on their surface.

19 . The system of claim 18 , wherein the activator comprises one or more antibodies selected from the group consisting of anti-CD2, anti-CD3, anti-CD28, and combinations thereof.

20 . The system of claim 19 , wherein the media comprises one or more cytokines selected from the group consisting of interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 7 (IL-7), interleukin 15 (IL-15), and combinations thereof.

Assignees

• Terumo Bct Inc

Inventors

• Nguyen Kim Thien Duy
• Startz Thomas Patrick
• Howard Alexander L

Classifications

• C12N2501/2302

  Interleukin-2 (IL-2) · CPC title

• C12M27/00

  Means for mixing, agitating or circulating fluids in the vessel (by introduction of gas C12M29/06, C12M29/14, mixing in general or mixers per se B01F; mixing in apparatus for chemical or physical processes B01J) · CPC title

• C12N2527/00

  Culture process characterised by the use of mechanical forces, e.g. strain, vibration · CPC title

• C12M23/44

  Multiple separable units; Modules · CPC title

• C12N2501/51

  B7 molecules, e.g. CD80, CD86, CD28 (ligand), CD152 (ligand) · CPC title