Automated CD34+ cell isolation of peripheral blood stem cell apheresis product

Spohn, Gabriele; Wiercinska, Eliza; Karpova, Darja; Bunos, Milica; Hümmer, Christiane; Wingenfeld, Eva; Sorg, Nadine; Poppe, Carolin; Huppert, Volker; Stuth, Juliane; Reck, Kristina; Essl, Mike; Seifried, Erhard; Bönig, Halvard

doi:10.1016/j.jcyt.2015.04.005

Cited by 41 publications

(31 citation statements)

References 20 publications

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“…However, there were differences in the recovery of target cell population and the depletion of CD3+ and CD19+ cells. These results are similar to those of Spohn and colleagues who also assessed the CliniMACS Prodigy for the selection of CD34+ cells.…”

Section: Discussionsupporting

confidence: 85%

“…The quantity of CD3+ cells in the CliniMACS Prodigy–selected products was greater than in the CliniMACS Plus–selected products both in our study and in that of Spohn and colleagues . However, the mean log depletion of CD3 cells we obtained with the CliniMACS Plus, 5.19 ± 0.35 log, was slightly greater than the mean values of 4.7, 4.8, and 5.1 reported by others using the CliniMACS Plus .…”

Section: Discussioncontrasting

confidence: 71%

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Preliminary evaluation of a highly automated instrument for the selection of CD34+ cells from mobilized peripheral blood stem cell concentrates

Stroncek¹,

Tran²,

Frodigh³

et al. 2015

Transfusion

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Background Cell selection is an important part of manufacturing cellular therapies. A new highly automated instrument, the CliniMACS Prodigy, was evaluated for the selection of CD34+ cells from mobilized peripheral blood stem cell (PBSC) concentrates using monoclonal antibodies conjugated to para-magnetic particles. Methods PBSCs were collected by apheresis from 36 healthy subjects given G-CSF or G-CSF plus plerixafor. CD34+ cells from 11 PBSC concentrates were isolated with the automated CliniMACS Prodigy and 25 with the semi-automated CliniMACS Plus Instrument. Results The proportion of CD34+ cells in the selected products obtained with the two instruments was similar; 93.6±2.6% for the automated and 95.7±3.3% for the semi-automated instrument (p > 0.05). The recovery of CD34+ cells from PBSC concentrates was less for the automated than the semi-automated instrument (51.4±8.2% versus 65.1±15.7%; p=0.019). The selected products from both instruments contained few and similar quantities of platelets and red blood cells. The depletion of CD3+ cells was less with the automated instrument (4.34±0.2 log depletion versus 5.20±0.35 log depletion; p < 1 × 10−6). Removal of platelets from PBSC concentrates by washing was associated with better CD34+ cell recovery. We explored the reasons for lower CD34+ cell recovery by the Prodigy and found that the non-selected cells for the Prodigy contained more platelets than those for the CliniMACS Plus. Conclusions CD34+ cells can be effectively selected from mobilized PBSC concentrates with the CliniMAC Prodigy, but the recovery of CD34+ cells and depletion of CD3+ cells was lower than with the semi-automated CliniMACS Plus Instrument.

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Section: Discussionsupporting

confidence: 85%

Section: Discussioncontrasting

confidence: 71%

Preliminary evaluation of a highly automated instrument for the selection of CD34+ cells from mobilized peripheral blood stem cell concentrates

Stroncek¹,

Tran²,

Frodigh³

et al. 2015

Transfusion

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“…Whether one of these strategies is superior to the depletion of all CD3+ T cells needs to be investigated in clinical trials. Further progress has been achieved in the establishment of nearly automatic CD34 selection via CliniMACS prodigy, but is still lacking for more complex depletion strategies like CD3/19 depletion …”

Section: Discussionmentioning

confidence: 99%

Optimization of individualized graft composition: CD3/CD19 depletion combined with CD34 selection for haploidentical transplantation

et al. 2016

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“…Various culture vessels, including G-Rex flasks (Wilson Wolf Manufacturing), cell differentiation bags and bioreactors have proven suitability for T-cell manufacturing [5][6][7]. Current procedures involve a variety of hands-on steps and transfer of cells between cultivation vessels, each bearing the risk of contamination, human errors and cell loss.To simplify the protocol and minimize potential risks during the process, the CliniMACS Prodigy [8] has been adapted to automate clinical-scale manufacturing of cell products [9][10][11]. This platform allows for magnetic beadbased cell separation followed by activation, transduction, multiple media-exchanges and washing steps with a single-use, closed tubing system ( Figure 1A, Figure 1B).…”

Section: Introductionmentioning

confidence: 99%

Automated manufacturing of chimeric antigen receptor T cells for adoptive immunotherapy using CliniMACS Prodigy

et al. 2016

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Novel cell therapies derived from human T lymphocytes are exhibiting enormous potential in early-phase clinical trials in patients with hematologic malignancies. Ex vivo modification of T cells is currently limited to a small number of centers with the required infrastructure and expertise. The process requires isolation, activation, transduction, expansion and cryopreservation steps. To simplify procedures and widen applicability for clinical therapies, automation of these procedures is being developed. The CliniMACS Prodigy (Miltenyi Biotec) has recently been adapted for lentiviral transduction of T cells and here we analyse the feasibility of a clinically compliant T-cell engineering process for the manufacture of T cells encoding chimeric antigen receptors (CAR) for CD19 (CAR19), a widely targeted antigen in B-cell malignancies. Using a closed, single-use tubing set we processed mononuclear cells from fresh or frozen leukapheresis harvests collected from healthy volunteer donors. Cells were phenotyped and subjected to automated processing and activation using TransAct, a polymeric nanomatrix activation reagent incorporating CD3/CD28-specific antibodies. Cells were then transduced and expanded in the CentriCult-Unit of the tubing set, under stabilized culture conditions with automated feeding and media exchange. The process was continuously monitored to determine kinetics of expansion, transduction efficiency and phenotype of the engineered cells in comparison with small-scale transductions run in parallel. We found that transduction efficiencies, phenotype and function of CAR19 T cells were comparable with existing procedures and overall T-cell yields sufficient for anticipated therapeutic dosing. The automation of closed-system T-cell engineering should improve dissemination of emerging immunotherapies and greatly widen applicability.

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Automated CD34+ cell isolation of peripheral blood stem cell apheresis product

Cited by 41 publications

References 20 publications

Preliminary evaluation of a highly automated instrument for the selection of CD34+ cells from mobilized peripheral blood stem cell concentrates

Preliminary evaluation of a highly automated instrument for the selection of CD34+ cells from mobilized peripheral blood stem cell concentrates

Optimization of individualized graft composition: CD3/CD19 depletion combined with CD34 selection for haploidentical transplantation

Automated manufacturing of chimeric antigen receptor T cells for adoptive immunotherapy using CliniMACS Prodigy

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