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Table 8 Alternative perfusion reactors for ACT

From: Lymphocyte expansion in bioreactors: upgrading adoptive cell therapy

 

Culture

Results

Characteristics

System

Cells

Medium

Stimulation strategy

Perfused medium

Inoculated cells/ml

Days

Yield

Purity

Functionality

Features

Disadvantages

Other ACT

Aastrom

TIL [132]

AIMV, RPMI 1640, HEPES, BME, 10% AB serum, 6000 IU/mL IL-2

Irradiated PBMC APCs; 6000 IU/mL IL2, OKT3

AIM V, 1% human serum, Glutamine 6000 IU/mL rhIL-2

5 × 106

14

up to 5.8 × 109 cells (1127 fold)

Populations nearly identical to static; 90% CD8+

Activity against HLA-A2+ matched tumor lines;

IFNγ secretion equal or higher than in static cultures

Slow medium exchange rates maintain a tissue-like microenvironment

Scaling is not available;

limited opportunity for in-process monitoring;

low surface area generates low yield

UCB [133]; DC [134]

ZRP

NK [91]

Alpha medium, glucose, 10% HS, glutamine, 1000 IU/mL IL2; proprietary activation cocktail.

Specific proprietary activating cocktail

NP

70 × 106

12–22

~ 14 fold

NK cell purity > 85%; T cells, B cells and NK T cells were below 2%

Cytotoxicity did not exceed 20% expression of activating receptors;

strong IFNγ expression

Directed laminar flow of medium, which allows an undisturbed cell/cell- and cell/surface-contact and minimizes cell stress

Efficiency and killing capacity are questioned

Other NK [19]

NK /γδT /CIK [135]

RPMI1640 complete medium (10% HS and 100 IU/mL IL2)

Irradiated K562- mb15–41BBL cells

NP

106

14

Static culturing resulted in higher cell counts than Z®-RP

Majority of expanded NK/γδT/CIK cells developed a CD56 bright phenotype

Static culturing resulted in higher cytotoxicity of NK/γδT/CIK than in dynamic culturing

Packed Bed

Tonsil tissue cells [136]

OPTI-MEM;

7.5% human AB serum

NP

OPTI-MEM

107

NP

Tissue formation

NP

NP

Architectural features typical of lymphoid organs

NP

DC [137]