Cell expansion

Inventors

VANG, Boah • NANKERVIS, Brian J. • Jones, Mark E.

Assignees

Terumo BCT Inc

Abstract

Embodiments described herein generally provide for expanding cells in a cell expansion system. The cells may be grown in a bioreactor, and the cells may be activated by an activator (e.g., a soluble activator complex). Nutrient and gas exchange capabilities of a closed, automated cell expansion system may allow cells to be seeded at reduced cell seeding densities, for example. Parameters of the cell growth environment may be manipulated to load the cells into a particular position in the bioreactor for the efficient exchange of nutrients and gases. System parameters may be adjusted to shear any cell colonies that may form during the expansion phase. Metabolic concentrations may be controlled to improve cell growth and viability. Cell residence in the bioreactor may be controlled. In embodiments, the cells may include T cells. In further embodiments, the cells may include T cell subpopulations, including regulatory T cells (Tregs), helper, naïve, memory, or effector, for example.

Core Innovation

The invention addresses expanding cells by preparing a plurality of cells for expansion, exposing the plurality of cells to an activator, and loading the plurality of cells into a bioreactor of a cell expansion system. The process includes feeding the plurality of cells according to a first feeding process that uses a first volume of fluid including media at a first flow rate into a first port during a first period and a second volume of the fluid including media at a second flow rate into a second port during at least a portion of the first period. The direction of the second flow rate is opposite the direction of the first flow rate, and the first flow rate and the second flow rate are different.

In a perfusion bioreactor implementation, the invention loads cells into a first fluid circulation path of a perfusion bioreactor. The perfusion bioreactor includes a first port and a second port and provides a second fluid circulation path associated with a second fluid flow path. Feeding is carried out by moving a first volume of fluid including a first media into the first port during a first period and moving a second volume of the same first media into the second port, where the direction into the bioreactor is opposite to the first direction and the second fluid flow rate is less than the first fluid flow rate.

The perfusion bioreactor implementation further includes circulating a third volume of a second media through an oxygenator to exchange one or more gasses in the cells expanding in the perfusion bioreactor. The cell expansion system is implemented as a closed, automated hollow-fiber cell expansion system that expands suspension (non-adherent) T cells, and it includes an oxygenator/gas transfer module and intracapillary and extracapillary spaces that support perfusion and gas exchange.

Claims Coverage

The provided material identifies two independent claims: one directed to expanding cells using a bioreactor feeding process with opposing flow directions and different flow rates, and another directed to expanding cells in a perfusion bioreactor with two circulation paths including oxygenator-mediated gas exchange. Across these independent claims, the main inventive features include a two-port feeding process with opposite flow directions and different flow rates, and a perfusion arrangement in which a separate circulation path sends media through an oxygenator to exchange gasses for cells expanding in the perfusion bioreactor.

Across the independent claims, the coverage centers on a feeding process that pumps media into first and second ports with opposite directions and different flow rates, and, for perfusion, an architecture with multiple circulation paths including oxygenator-mediated exchange of one or more gasses for cells expanding in the perfusion bioreactor.

Stated Advantages

Documented Applications