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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]