From: Lymphocyte expansion in bioreactors: upgrading adoptive cell therapy
 | Protocol features | Starting material | Reactor configuration | ||||||||||
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Author –Year | IL-2 [IU/mL] | Stimulation strategy | Medium | Serum and supplements | Source | Seed concentration [cells/mL] | Bag volume [L] | Culture volume [mL] | System | Rocks per minute | Air flow [L/min] | Rocking Angle [°] | Feeding strategy |
T CELLS | |||||||||||||
Hami [98] - 2004 | Useda | CD3 and CD28 beads | Xvivo 15 | – | CD3+ T cells from PBMC | – | 20 | – | Wave Bioreactor System 20XE | – | – | – | Perfusion |
Tran [66] - 2007 | 50 | Irradiated PBMCs (APCs) | RPMI | 10% FBS; HEPES, GLN and Glucose | CD4+ T cells from PBMC |  | – | – | Wave bioreactor system 2/10 EH | 10–12 | 0.1 | 4 | Perfusion: Media to keep GLN at 2 mM and glucose > 2 g/L. |
Hollyman [99] - 2009 | 100–500 | Preb - CD3/CD28 beads | Xvivo 15 | 5% AB | CD3+ from PBMCs | – | 2 | – | WAVE EHT Bioreactor | 6–15 | – |  | Perfusion: Volume increased over 24 h periods (200–1600 mL/day) |
Janas [100] - 2015 | 20 [ng/mL] | Pre - CD3/CD28 beads | Xvivo 10 | 5% HS; GLN | T cells from PBMCs | 5.0 × 106 | – | 1000 | W25 or W5 Xuri cell expansion system | 15 | – | 6 | Perfusion: < 2 × 106 cells/mL–0 mL/day; 2–10 × 106 cells/mL–500 mL/day; 10–15 × 106 cells/mL–750 ml/day; > 15 × 106 cells/mL–1000 mL/day |
Vavrova [101] - 2016 | 20 | Pre - Ag-mDCs (APCs); CD3/CD28 beads | RPMI | 5% AB; GLN, Ne AAs, BME, Pyruvate | T cells from PBMCs | – | 2 | – | WAVE bioreactor 2/10 system | 6 | – | 6 | Media fed: maintain cell concentration in the 0.5–1 × 106 cells/mL range |
O’hanlon [102] - 2017 | 200 | Pre PHA | IMDM | 10% AB; GLN and glucose | T cells from PBMCs | 2.5–5.0 × 105 | 2 | 1000 | Wave 2/10 (Xuri W5) | 5–10 | – | – | Perfusion: Culture days 1–2: 250 mL; Culture days 3–5: 500 mL |
 McCartney [57] - 2019 | 350 | – | Xuri T CEM | 5% AB | T cells from PBMCs | – | 2 | 1000 | Xuri Cell Expansion System | 10 | – | 6 | Perfusion: < 2 × 106 cells/mL–0 mL/day; 2–10 × 106 cells/mL–500 mL/day; 10–15 × 106 cells/mL–750 ml/day; > 15 × 106 cells/mL–1000 mL/day |
Smith [103] - 2019 | 200–500 | Pre anti CD3/CD28/CD2 | Xuri T CEM | 5% HS | Tcells from PBMCS | 1.0 × 106 | 2 | – | Xuri Cell Expansion System W25 | 10 | – | 6 | Perfusion: < 2 × 106 cells/mL–0 mL/day; 2–10 × 106 cells/mL–500 mL/day; 10–15 × 106 cells/mL–750 ml/day; > 15 × 106 cells/mL–1000 mL/day |
NK CELLS | |||||||||||||
Sutlu [94] - 2010 | 500 | OKT3 | SCGM | 5% HS | PMBC | 2.0 × 106 | – | from 800 | Wave Bioreactor System 2/10 | 6 | 0.1 | 6 | Media fed: 300 mL/day when 3 e6 cells/mL when 7 e6 cells/mL, 500 mL/day; 1 e7 cells/mL, 750 mL/day; 2.5 e7, 1 L/day. |
Spanholtz [104] - 2011 | Useda | GM-CSF. G-CSF, IL-6, IL-7, IL-15 | GBGM | 10% HS | CD34+ UCB | 1.0 × 106 | – | from 250 | WAVE Bioreactor System 2/10 and BIOSTATH CultiBag RM | 10 | 0.1–0.2 | 6 | Media addition to adjust cell density |
 Rujkijyanont [105] - 2013 | 500 | CD56- (APCs); IL15 OKT3 | SCGM | 5% AB | CD56+ from PBMCs | 1.0 × 106 | 2–20 | from 200 | WAVE Bioreactor | 5–9 | – | – | Media addition to adjust cell density |
Lapteva [106] - 2014 | 500 | K562-41BBL-mbIL-15 (APCs) | SCGM | 10% FBS | CD56+ from PBMCs | 2.0 × 105 | – | – | WAVE Bioreactor | 6 | – | 6 | – |
Meng [97] - 2018 | Useda | Pre OK-432 | Xvivo 15 | 1% AP | PBMC | – | 3 | 3000 | GE Xuri W25 | 7 | – | 6 | Perfusion (parameters not specified) |
TILs | |||||||||||||
Sadeghi [107] - 2011 | 600 | PBMCs (APCs); OKT3 | RPMI | 5% AB; GLN 12 mM, 25 mM HEPES; BME | TIL | 5–10.0 × 107 (TOTAL) | 2 | 1000 | Wave Bioreactor System 2/10 (GE) | 10 | – | 6 | Perfusion: 350–1000 mL/day to maintain glucose and GLN in a range of 1.5–2 g/L and ~ 2–4 mM, respectively. |
 Somerville [64] - 2012 | 3000 | Pre – allogenic APCs, anti-CD3 | AIMV | 5% AB; 0,02% pluronic | TIL/PBL | – | – | 1500 | WAVE bioreactor 2/10 system | 7 | – | 6 | Perfusion: maintain glucose concentration at ~ 170 mg/dL. |
Donia [108] - 2014 | 6000 | Pre - allogeneic APCs, antiCD3 | AIMV | Pluronic | TIL | – | 10 |  | WAVE bioreactor 2/10 system | 10 | 0.2 | 6 | 1000–4000 mL/day |