System and methods for immune cells expansion and activation in large scale
Inventors
Raviv, Lior • BACHAR, Shirley • ROBERMAN, Dorina
Assignees
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Publication Number
US-12291702-B2
Publication Date
2025-05-06
Expiration Date
Abstract
This invention discloses a three-dimensional (3D) bioreactor for large scale expansion of immune cells and methods of use. The 3D bioreactor comprising at least one packed bed chamber comprising at least one porous scaffold; at least one porous scaffold coated with one or more extra cellular matrix protein (ECM); at least one container comprising a fluid media, the fluid media is configured to flow through said packed bed chamber with at least one porous coated scaffold; and at least one population of immune cells suspended in the fluid media, wherein, the at least one porous scaffold coated with said ECM is creates a stationary niche having low shear forces that imitate the natural growth environment of the immune cells and allows expansion of the immune cells population that flow through the coated porous scaffold in large scale.
Core Innovation
The invention provides a three-dimensional (3D) bioreactor for large scale expansion of immune cells using at least one packed bed chamber. A porous scaffold is positioned so that fluid media containing a population of immune cells flows through the packed bed chamber and through the porous scaffold, and the porous scaffold is coated with one or more extra cellular matrix protein (ECM). The ECM-coated porous scaffold creates a stationary niche having low shear forces that imitate the natural growth environment of the immune cells, and its porosity allows expansion in large scale without immobilizing the immune cells.
In an additional independent embodiment, the invention provides a 3D bioreactor for large scale expansion and activation of immune cells population using at least one porous Antigen Presenting Cell Mimetic Scaffold (APC-MS) coated with one or more ECM. Fluid media having at least one population of immune cells suspended in the container flows through the porous APC-MS coated with ECM, and the porous APC-MS coated with ECM creates a stationary microenvironment having low shear forces that imitate the natural growth environment of the immune cells.
The method embodiment describes inserting at least one porous scaffold into at least one packed bed chamber, coating the porous scaffold with one or more ECM, and circulating cell-containing fluid media through the packed bed chamber and through the ECM-coated porous scaffold. The ECM-coated scaffold creates a stationary niche with low shear forces imitating natural growth environment and allows large scale expansion without immobilizing immune cells, and dependent method features include using an immune cell activator associated with ECM for expansion and activation, genetically modifying a population of immune cells by adding one or more gene modifying agents to fluid media in the bioreactor, and harvesting immune cells and reseeding genetically modified cells into the same or a different bioreactor.
Claims Coverage
The provided material includes three independent claims, covering a 3D packed-bed bioreactor system and an associated method for large scale immune-cell expansion, with a separate embodiment emphasizing expansion and activation via a porous APC-MS scaffold. Across the independent claims, the inventive features center on ECM-coated porous scaffolds inside packed bed chambers producing a stationary low-shear niche that supports large scale expansion without immobilizing immune cells.
Packed bed chamber with ECM-coated porous scaffold for stationary low-shear expansion
A 3D bioreactor comprising at least one packed bed chamber and at least one porous scaffold surrounded by the packed bed chamber, wherein the porous scaffold is coated with one or more extra cellular matrix protein (ECM); and fluid media having at least one population of immune cells suspended in the fluid media flows through the packed bed chamber and the porous scaffold, wherein the ECM-coated porous scaffold creates a stationary niche having low shear forces that imitate the natural growth environment of the immune cells and has a porosity which allows expansion in large scale without immobilizing the immune cells.
Circulating through packed bed chamber and ECM-coated scaffold to create stationary low-shear niche for expansion
A method for large scale expansion of immune cells in a 3D bioreactor comprising inserting at least one porous scaffold into at least one packed bed chamber, coating the porous scaffold with one or more extra cellular matrix protein (ECM), and circulating a fluid media having at least one population of immune cells suspended in the fluid media so the fluid media flows through the packed bed chamber and the ECM-coated porous scaffold, wherein the ECM-coated porous scaffold creates a stationary niche having low shear forces that imitate the natural growth environment and has a porosity allowing expansion in large scale without immobilizing the immune cells.
Porous APC-MS coated with ECM to provide stationary low-shear microenvironment for expansion and activation
A 3D bioreactor for large scale expansion and activation of immune cells population comprising at least one packed bed chamber and at least one porous Antigen Presenting Cell Mimetic Scaffold (APC-MS) surrounded by the packed bed chamber, wherein the porous APC-MS is coated with one or more extra cellular matrix protein (ECM); and fluid media containing a population of immune cells flows through the porous APC-MS coated with ECM, wherein the porous APC-MS coated with ECM creates a stationary microenvironment having low shear forces that imitate the natural growth environment and has a porosity allowing large scale expansion and/or activation without immobilizing the immune cells.
Overall, the independent claims define a packed-bed 3D bioreactor where immune-cell-containing fluid media flows through ECM-coated porous scaffolds that create a stationary low-shear niche for large scale expansion without immobilization, and a related embodiment where the porous scaffold is specifically an APC-MS to provide a stationary low-shear microenvironment supporting large scale expansion and/or activation.
Stated Advantages
Allows large scale expansion of immune cells without immobilizing the immune cells.
Creates a stationary niche having low shear forces that imitate the natural growth environment of the immune cells.
Allows large scale expansion and/or activation of immune cells without immobilizing the immune cells.
Documented Applications
Large scale expansion of immune cells in a 3D bioreactor using ECM-coated porous scaffolds within packed bed chambers.
Large scale expansion and activation of immune cells in a 3D bioreactor using a porous Antigen Presenting Cell Mimetic Scaffold (APC-MS) coated with ECM.
Expansion and activation method using an immune cell activator associated with the ECM-coated porous scaffold.
Genetic modification of a population of immune cells in or associated with the 3D bioreactor workflow by adding gene modifying agents to fluid media containing suspended immune cells.
Harvesting immune cells and reseeding genetically modified cells into the same or a different bioreactor as part of an expansion and modification workflow.
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