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Table 5 Protocol features in Hollow fiber reactors

From: Lymphocyte expansion in bioreactors: upgrading adoptive cell therapy

Author - Year

Pre stimulaiton

Cell culture

IC

Starting material

Culture system

Medium

Stimulation

Serum and supplements

Source

Inoculation [cells/reactor]

Volume [mL]

Reactor

Fibers

Cut off [kDa]

Surface area [cm2]

Perfusion flow [mL/min]

Control

T cells

 Lamers [124] - 1994

IL2, PHA or CD3 mAb

AIMV

IL2

10% AB

Glutamine and glucose + RPMI

PBMC

109

NP

Immuno*star 4000

10,000

10

NP

50

Control glucose at 1.5 g/L

 Lamers [125] - 1999

IL2, PHA

AIMV

IL2

NP

Glutamine and glucose + RPMI

PBMC

1.7–3.1 × 108

100

Immuno*star 4000

10,000

10

NP

50

Control glucose at 2 g/l; control lactate levels

 Liu [126] - 1999

Anti CD3/CD8 mAb

CCM

IL2

1% AB

Medium

CD4+ and CD8+ from PBMC

2–8 × 107

NP

Cellco Cellmax

NP

NP

NP

NP

Control glucose at 50–100 mg/dL

 Trickett [127] - 2002

IL2, Anti CD3 or PHA

AIMV

CD3/CD28 beads or PHA

5 to 2% FBS

Medium

HIV infected CD4+ cells from PBMC

2–3 107

NP

Cellmax Quad

NP

NP

NP

50

Keep glucose above 50% of the baseline value

 De Bartolo [114] - 2007

PHA

DMEM

NP

10% FBS

Medium

PBMC

8 × 107

24

PEEK-WC-HF

NP

NP

128

5 to 10

NP

 Curcio [128] - 2012

PHA

DMEM

PHA

10% FBS

Medium

PBMC

8 × 107

25

Parallel-HFMBR

NP

NP

128

2–10

Adjust concentrations to number of cells

 Curcio [128] - 2012

PHA

DMEM

PHA

10% FBS

Medium

PBMC

8 × 107

35

Crossed-HFMBR

NP

NP

NP

2–10

Adjust concentrations to number of cells

 Nankervis [111] - 2018

IL2, Anti CD3/CD8 beads + IL7

NP

IL2; IL7

NP

Cells

PBMC

NP

100

Quantum 1st generation protocol

11,520

17

NP

EC: 100

IC: 1

NP

 Nankervis [111] - 2018

IL2, Anti CD3/CD8 beads

NP

IL2

NP

Cells

PBMC

NP

100

Quantum 2nd generation protocol

11,520

17

NP

Max. 300

NP

 Coeshott [112] - 2019

IL2, Anti CD3/CD8 beads

PRIME-XV

NP

NP

Cells

PBMC

3.0–8.5 × 107

124

Quantum

11,520

17

21,000

Max. 300 (IC)

Remove lactate

TIL

 Knazek [78] - 1990

IL2, Autol. LAK supern. and serum

AIMV

IL2 OR LAK supernatant. + HS

Glucose and glutamine

Medium

Melanoma

NP

50

Cellmax 100

8000

 

11,000

40–300n

Control glucose at

1–1.5 g/L

 Hillman [115] - 1994

IL2, TNFa

AIMV

IL2

10% AB

RPMI

Kidney tumors

5–30 × 108

30

IMMUNO*STAR® 1000 Cell Expander

NP

10

3000

EC: 2

IC: 200

Control glucose

 Freedman [119] - 1994

IL2

AIMV

IL2

NP

Medium

Ascites/pleural effusions/solid tumors

109

NP

Cellmax 100

8000

4

23,000

60–300

Control glucose

 Lewko [129] - 1994

IL2, Autol. LAK supern. and serum

AIMV

IL2

NP

Medium

Tumor

1–2 × 109

NP

Cellmax 100

NP

4

23,000

NP

Control glucose between 1.0–1.5 g/L

 Lewko [117] - 2000

IL2, Autol. LAK supern. and serum

AIMV

IL2

NP

Medium

Tumor

1–2 × 109

NP

Cellmax 100

NP

NP

23,000

NP

Control glucose between 1.0–1.5 g/L

 Freedman [130] - 2000

IL2

AIMV

IL2

NP

Medium

Tumor samples

1–2 × 109

NP

Cellmax 100

NP

NP

NP

NP

NP

 Malone [118] - 2001

IL2, OKT3

AIMV

IL2

Glutamine

Medium

Tumor samples

4–6 × 108

100

Celco - not specified

NP

30–150

2200

NP

Keep lactate below 1000 units/mL

PBL

 Pan [120] - 1999

IL2, OKT3

AIMV

IL2

5% FBS, glutamine

Medium

PBL

5–9.3 × 107

NP

Cellmax Quad pump station

NP

NP

NP

NP

Controlling lactate levels

 Shankar [121] - 1997

OKT3

AIMV

IL2

5% FBS, glutamine

Medium

PBL

5 × 107

11.4

Cellmax Artificial Capillary

NP

NP

NP

NP

Keep lactate below 0.5 mg/mL

 Stroncek [122] - 1999

OKT3

AIMV

IL2

5% FBS, glutamine

Medium

PBL

108

11

Cellmax Artificial Capillary

NP

NP

NP

NP

NP

  1. NP Not published