System and methods for immune cells expansion and activation in large scale

A method for large scale expansion of immune cells in a three-dimensional (3D) bioreactor, the method comprising the steps of:

• a inserting at least one porous scaffold into at least one packed bed chamber;
• b. coating said at least one porous scaffold with one or more extra cellular matrix protein (ECM);
• c. circulating a fluid media having at least one population of immune cells suspended in said fluid media contained in at least one container surrounding said at least one packed bed chamber, said fluid media having at least one population of immune cells suspended in said fluid media flows through said at least one packed bed chamber and said at least one porous scaffold coated with one or more ECM;
• and
• wherein, said at least one porous scaffold coated with one or more ECM creates a stationary niche having low shear forces that imitate the natural growth environment of said population of immune cells;
• wherein said at least one porous scaffold coated with one or more ECM has a porosity which allows expansion of said at least one population of immune cells that flows said at least one porous scaffold coated with one or more ECM in large scale without immobilizing said at least one population of immune cells;
• and
• wherein said immune cells are one of Jurkat, T2 cells, K562 cells, Raji, U973, THP-1, HL-60, Peripheral Blood Mononuclear Cells (PBMC), polymorphonuclear cells (PMN), conventional and unconventional T cells, B cells, B cell Hybridomas, CAR-B, NKT cells, CAR-NKT, gamma-delta T (gdT), CAR-gdT, NK cells, CAR-NK, and combinations thereof.

A three-dimensional (3D) bioreactor for large scale expansion and activation of immune cells population the 3D bioreactor comprising:

• at least one packed bed chamber;
• at least one porous Antigen Presenting Cell Mimetic Scaffold (APC-MS) surrounded by said at least one packed bed chamber wherein said at least one porous APC-MS is coated with one or more extra cellular matrix protein (ECM);
• at least one container surrounding said at least one packed bed chamber;
• and
• a fluid media having at least one population of immune cells suspended in said fluid media contained in said at least one container;
• wherein said fluid media having at least one population of immune cells suspended in said fluid media flows through said at least one porous APC-MS coated with one or more ECM;
• wherein, said at least one porous APC-MS coated with one or more ECM creates a stationary microenvironment having low shear forces that imitate the natural growth environment of said at least one population of immune cells;
• wherein said at least one porous APC-MS coated with one or more ECM has a porosity which allows large scale expansion and/or activation of said at least one population of immune cells that flow through said at least one porous APC-MS coated with one or more ECM without immobilizing said at least one population of immune cells;
• and
• wherein said immune cells are one of Jurkat, T2 cells, K562 cells, Rajii, U973, THP-1, HL-60, Peripheral Blood Mononuclear Cells (PBMC), polymorphonuclear cells (PMN), conventional and unconventional T cells, B cells, B cell Hybridomas, CAR-B, NKT cells, CAR-NKT, gamma-delta T (gdT) cells, CAR-gdT, NK cells, CAR-NK, and combinations thereof.