Manufacturing T cells in hollow fiber membrane bioreactors changes their programming and enhances their potency

Yoo, Seung Mi; Lau, Vivian Wing Chong; Aarts, Craig; Bojović, Bojana; Steinberg, Gregory R.; Hammill, Joanne A.; Dvorkin‐Gheva, Anna; Ghosh, Raja; Bramson, Jonathan L.

doi:10.1080/2162402x.2021.1995168

Cited by 3 publications

(2 citation statements)

References 40 publications

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“…Another crucial step in generating biotherapeutics for clinical use is selecting an appropriate bioreactor platform (Adlerz et al., 2020; Yoo et al., 2021). Among the available options, hollow‐fibre bioreactors (HFBs) stand out as closed‐loop systems that offer several benefits; these include improved control over critical process parameters, reduced maintenance and reduced hands‐on time, ultimately leading to lower costs and better product quality (Bröker et al., 2019; Egger et al., 2017; Gobin et al., 2021; Rohde et al., 2019; Yoo et al., 2021). In addition, HFBs allow for high‐density cell cultivation, making it possible to generate large quantities of biotherapeutics continuously and rapidly (Estes et al., 2022).…”

Section: Discussionmentioning

confidence: 99%

A clinically relevant large‐scale biomanufacturing workflow to produce natural killer cells and natural killer cell‐derived extracellular vesicles for cancer immunotherapy

St‐Denis‐Bissonnette,

Cummings,

Qiu

et al. 2023

J of Extracellular Vesicle

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Natural killer cell‐derived extracellular vesicles (NK‐EVs) have shown promising potential as biotherapeutics for cancer due to their unique attributes as cytotoxic nanovesicles against cancer cells and immune‐modulatory activity towards immune cells. However, a biomanufacturing workflow is needed to produce clinical‐grade NK‐EVs for pre‐clinical and clinical applications. This study established a novel biomanufacturing workflow using a closed‐loop hollow‐fibre bioreactor to continuously produce NK‐EVs from the clinically relevant NK92‐MI cell line under serum‐free, Xeno‐free and feeder‐free conditions following GMP‐compliant conditions. The NK92 cells grown in the bioreactor for three continuous production lots resulted in large quantities of both NK cell and NK‐EV biotherapeutics at the end of each production lot (over 109 viable cells and 1013 EVs), while retaining their cytotoxic payload (granzyme B and perforin), pro‐inflammatory cytokine (interferon‐gamma) content and cytotoxicity against the human leukemic cell line K562 with limited off‐target toxicity against healthy human fibroblast cells. This scalable biomanufacturing workflow has the potential to facilitate the clinical translation of adoptive NK cell‐based and NK‐EV‐based immunotherapies for cancer with GMP considerations.

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Section: Discussionmentioning

confidence: 99%

A clinically relevant large‐scale biomanufacturing workflow to produce natural killer cells and natural killer cell‐derived extracellular vesicles for cancer immunotherapy

St‐Denis‐Bissonnette,

Cummings,

Qiu

et al. 2023

J of Extracellular Vesicle

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show abstract

“…HFBRs can be made into an automatic system with single use functionally closed cell culture consumable set, such as the Quantum Cell Expansion System. Studies have shown that the Quantum Cell Expansion System can produce large quantities of functional T-cells at clinical dosage levels [46] with increased potency [47].…”

Section: Hollow Fibre Membrane Bioreactors For Car-t Immunotherapymentioning

confidence: 99%

Membrane Applications in Autologous Cell Therapy

Martin

Lei

Zeng³

et al. 2022

Membranes

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Stem cell and cell therapies, particularly autologous cell therapies, are becoming a common practice. However, in order for these technologies to achieve wide-scale clinical application, the prohibitively high cost associated with these therapies must be addressed through creative engineering. Membranes can be a disruptive technology to reshape the bioprocessing and manufacture of cellular products and significantly reduce the cost of autologous cell therapies. Examples of successful membrane applications include expansions of CAR-T cells, various human stem cells, and production of extracellular vesicles (EVs) using hollow fibre membrane bioreactors. Novel membranes with tailored functions and surface properties and novel membrane modules that can accommodate the changing needs for surface area and transport properties are to be developed to fulfil this key role.

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Enriching central memory T cells using novel bioreactor design for T cell manufacturing

Chen,

Prabhu,

Bin Abdul Rahim

et al. 2025

Cytotherapy

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Manufacturing T cells in hollow fiber membrane bioreactors changes their programming and enhances their potency

Cited by 3 publications

References 40 publications

A clinically relevant large‐scale biomanufacturing workflow to produce natural killer cells and natural killer cell‐derived extracellular vesicles for cancer immunotherapy

A clinically relevant large‐scale biomanufacturing workflow to produce natural killer cells and natural killer cell‐derived extracellular vesicles for cancer immunotherapy

Membrane Applications in Autologous Cell Therapy

Enriching central memory T cells using novel bioreactor design for T cell manufacturing

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