ADD a bunch of references to the bioreactor section
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@ -1721,6 +1721,84 @@ CONCLUSIONS: We developed a simplified, semi-closed system for the initial selec
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publisher = {Hindawi Limited},
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}
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@Article{Hollyman2009,
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author = {Daniel Hollyman and Jolanta Stefanski and Mark Przybylowski and Shirley Bartido and Oriana Borquez-Ojeda and Clare Taylor and Raymond Yeh and Vanessa Capacio and Malgorzata Olszewska and James Hosey and Michel Sadelain and Renier J. Brentjens and Isabelle Rivi{\`{e}}re},
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journal = {Journal of Immunotherapy},
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title = {Manufacturing Validation of Biologically Functional T Cells Targeted to {CD}19 Antigen for Autologous Adoptive Cell Therapy},
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year = {2009},
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month = {feb},
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number = {2},
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pages = {169--180},
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volume = {32},
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doi = {10.1097/cji.0b013e318194a6e8},
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publisher = {Ovid Technologies (Wolters Kluwer Health)},
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}
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@Article{Brentjens2013,
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author = {R. J. Brentjens and M. L. Davila and I. Riviere and J. Park and X. Wang and L. G. Cowell and S. Bartido and J. Stefanski and C. Taylor and M. Olszewska and O. Borquez-Ojeda and J. Qu and T. Wasielewska and Q. He and Y. Bernal and I. V. Rijo and C. Hedvat and R. Kobos and K. Curran and P. Steinherz and J. Jurcic and T. Rosenblat and P. Maslak and M. Frattini and M. Sadelain},
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journal = {Science Translational Medicine},
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title = {{CD}19-Targeted T Cells Rapidly Induce Molecular Remissions in Adults with Chemotherapy-Refractory Acute Lymphoblastic Leukemia},
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year = {2013},
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month = {mar},
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number = {177},
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pages = {177ra38--177ra38},
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volume = {5},
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doi = {10.1126/scitranslmed.3005930},
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publisher = {American Association for the Advancement of Science ({AAAS})},
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}
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@Article{Zhu2018,
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author = {Fenlu Zhu and Nirav Shah and Huiqing Xu and Dina Schneider and Rimas Orentas and Boro Dropulic and Parameswaran Hari and Carolyn A. Keever-Taylor},
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journal = {Cytotherapy},
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title = {Closed-system manufacturing of {CD}19 and dual-targeted {CD}20/19 chimeric antigen receptor T cells using the {CliniMACS} Prodigy device at an academic medical center},
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year = {2018},
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month = {mar},
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number = {3},
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pages = {394--406},
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volume = {20},
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doi = {10.1016/j.jcyt.2017.09.005},
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publisher = {Elsevier {BV}},
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}
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@Article{Kaiser2015,
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author = {A D Kaiser and M Assenmacher and B Schröder and M Meyer and R Orentas and U Bethke and B Dropulic},
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journal = {Cancer Gene Therapy},
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title = {Towards a commercial process for the manufacture of genetically modified T cells for therapy},
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year = {2015},
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month = {jan},
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number = {2},
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pages = {72--78},
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volume = {22},
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doi = {10.1038/cgt.2014.78},
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publisher = {Springer Science and Business Media {LLC}},
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}
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@Article{Bunos2015,
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author = {M. Bunos and C. Hümmer and E. Wingenfeld and N. Sorg and V. Pfirrmann and P. Bader and E. Seifried and H. Bönig},
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journal = {Vox Sanguinis},
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title = {Automated isolation of primary antigen-specific T cells from donor lymphocyte concentrates: results of a feasibility exercise},
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year = {2015},
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month = {may},
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number = {4},
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pages = {387--393},
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volume = {109},
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doi = {10.1111/vox.12291},
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publisher = {Wiley},
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}
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@Article{Somerville2012,
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author = {Robert P.T. Somerville and Mark E. Dudley},
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journal = {{OncoImmunology}},
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title = {Bioreactors get personal},
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year = {2012},
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month = {nov},
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number = {8},
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pages = {1435--1437},
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volume = {1},
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doi = {10.4161/onci.21206},
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publisher = {Informa {UK} Limited},
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}
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@Comment{jabref-meta: databaseType:bibtex;}
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@Comment{jabref-meta: grouping:
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@ -747,6 +747,8 @@ cytokine release properties and ability to resist exhaustion\cite{Wang2018,
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Yang2017}, and no method exists to preferentially expand the CD4 population
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compared to state-of-the-art systems.
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\subsection{cell sources in T cell manufacturing}
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\subsection{methods to scale T cells}
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In order to scale T cell therapies to meet clinical demands, automation and
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@ -754,24 +756,26 @@ bioreactors will be necessary. To this end, there are several choices that have
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found success in the clinic.
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The WAVE bioreactor (GE Healthcare) is the choice of expansion for many clinical
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applications [5,45,64]. It is part of a broader class of bioreactors that
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consist of rocking platforms that agitate a bag filled with media and cells.
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Importantly, it has built-in sensors for measuring media flow rate, carbon
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dioxide, oxygen, pH, and nutrient consumption which enables automation.
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Unfortunately, in some settings this is not considered scalable as only one bag
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per bioreactor is allowed at once\cite{Roddie2019}.
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applications\cite{Brentjens2011, Hollyman2009, Brentjens2013}. It is part of a
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broader class of bioreactors that consist of rocking platforms that agitate a
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bag filled with media and cells. Importantly, it has built-in sensors for
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measuring media flow rate, carbon dioxide, oxygen, pH, and nutrient consumption
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which enables automation. Unfortunately, in some settings this is not considered
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scalable as only one bag per bioreactor is allowed at once\cite{Roddie2019}. The
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other disadvantage with the WAVE system is that it keeps cells far apart by
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design, which could have negative impact on cross-talk, activation, and
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growth\cite{Somerville2012}.
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% BACKGROUND find clinical trials (if any) that use this
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Alternatively, the CliniMACS Prodigy (Miltenyi) is an all-in-one system that is
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a fully closed system that removes the need for expensive cleanrooms and
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associated personnel. It contains modules to perform transduction, expansion,
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and washing. This setup also implies that fewer mistakes and handling errors
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will be made, since many of the steps are internal to the machine. Initial
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investigations have shown that it can yield T cells doses required for clinical
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use.
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% https://reader.elsevier.com/reader/sd/pii/S1465324917307041?token=CF7C833CF6E0A7D5E003703A845A51066D028D5BF605792595DCF8D540B23933F4B856A0A9881C6DDEFE0C38D220A768&originRegion=us-east-1&originCreation=20210802022804
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At the time of writing, several clinical trial are underway which use the
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CliniMACS, although mostly for stem-cell based cell treatments.
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associated personnel\cite{Kaiser2015, Bunos2015}. It contains modules to perform
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transduction, expansion, and washing. This setup also implies that fewer
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mistakes and handling errors will be made, since many of the steps are internal
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to the machine. Initial investigations have shown that it can yield T cells
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doses required for clinical use\cite{Zhu2018}. At the time of writing, several
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clinical trial are underway which use the CliniMACS, although mostly for
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stem-cell based cell treatments.
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Finally, another option that has been investigated for T cell expansion is the
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Grex bioreactor (Wilson Wolf). This is effectively a tall tissue-culture plate
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@ -782,8 +786,9 @@ to plates and flasks normally used for small-scale research, the important
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difference is that its larger size requires fewer interactions and keeps the
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cells at a higher nutrient concentration for longer periods of time. However, it
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is still a an open system and requires manual (by default) interaction from an
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operator to load, feed, and harvest the cell product. Grex bioreactors have
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been using to grow \glspl{til} [58] and virus-specific T cells [61].
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operator to load, feed, and harvest the cell product. Grex bioreactors have been
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using to grow \glspl{til}\cite{Jin2012} and virus-specific T
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cells\cite{Gerdemann2011}.
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\subsection{overview of T cell quality}
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