Expanding cells in a bioreactor

Inventors

NANKERVIS, Brian J. • HILL, Domicinda M. • 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), for example.

Core Innovation

The invention relates to confining cells within a hollow fiber device by loading the cells and moving them into an intracapillary side or an extracapillary side. The moving includes activating a first pump at a first pump rate to flow a first fluid in a first flow direction to move the cells into the selected side, and after the cells are moved, retaining the cells within that side.

The retaining is performed by simultaneously activating a second pump to flow fluid in a second direction opposite to the first direction. The first pump and the second pump are simultaneously activated, and the first pump rate and the second pump rate are complementary rates, so that counterflow is sufficient to retain the cells within the hollow fiber device.

The invention is also expressed as confining cells or large molecular weight solutes in a chamber by flowing a first fluid along a first flow path while generating counter-flow in an opposite direction in the same flow path. In this chamber-based form, the first pump and the second pump are simultaneously activated with complementary pump rates so that counterflow is sufficient to retain the cells or solutes in a portion of the chamber.

The document further associates confinement with a hollow fiber bioreactor or a hollow fiber device configuration and controlling an environment inside the device to expand, treat, or grow cells. It also describes closed, automated hollow-fiber cell expansion systems that activate and expand T cells, with feed-and-retain operation and control of metabolite levels, including lactate, through adjustable media addition or flow rates.

Claims Coverage

The independent claims cover methods for confining cells, and in one instance large molecular weight solutes, using two simultaneously activated pumps with complementary pump rates. The main inventive features are counterflow confinement in a hollow fiber device or a chamber, with claim-dependent refinements for intracapillary side, extracapillary side, or a chamber portion.

Across the independent claims, the core claim coverage centers on confining cells by generating counterflow with two pumps simultaneously activated at complementary pump rates. One claim applies the confinement to cells loaded into a hollow fiber device with retention in an intracapillary or extracapillary side, and other claims apply counterflow confinement to a chamber portion for cells, with one also including large molecular weight solutes.

Stated Advantages

Documented Applications