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Volume 20, Issue 1, Pages (January 2017)

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1 Volume 20, Issue 1, Pages 13-17 (January 2017)
Achieving Efficient Manufacturing and Quality Assurance through Synthetic Cell Therapy Design  Yonatan Y. Lipsitz, Patrick Bedford, Anthony H. Davies, Nicholas E. Timmins, Peter W. Zandstra  Cell Stem Cell  Volume 20, Issue 1, Pages (January 2017) DOI: /j.stem Copyright © 2017 Elsevier Inc. Terms and Conditions

2 Figure 1 Therapeutics Designed from Readily Available Cell Types Can Fail to Address Unmet Clinical Need Therapeutics may lack a needed function (the function of protein “C”) or exist in an undesirable gene regulatory network state (state “ABC”). Tools to engineering cells include gene manipulation (e.g., inserting gene “C” into the cell) or cell state manipulation (cytokine-induced shift to gene regulatory network “BCDE”). These strategies can resolve CTP challenges including designing new CTP functionality (such as a new receptor on an immune cell for a cancer-specific antigen), simplifying quality assessment by indicating or selecting for a desired cell population in a heterogeneous culture, and enhancing cell manufacturability by generating universal-donor or robustly expanding cell populations. These modifications are illustrated in red. Cell Stem Cell  , 13-17DOI: ( /j.stem ) Copyright © 2017 Elsevier Inc. Terms and Conditions

3 Figure 2 Complexity and Extent of Synthetic Properties of CTPs Compared to Other Therapeutics Synthetic cell therapy via cell engineering represents a logical next step to which other therapeutic types have progressed. Just as small-molecule drugs progressed from naturally occurring products through synthesized drugs to synthetic, biomaterial integrated drugs, so too have cell therapies progressed from minimally manipulated cells to cultured cells, and now to engineered cells. A key difference between these strategies is the increased complexity of engineered cells relative to small-molecule drugs and most biologics. However, ample precedent for the progression to synthetic therapeutics has been set in other advanced therapies including a variety of antibody-drug conjugates and engineered protein products. Cell Stem Cell  , 13-17DOI: ( /j.stem ) Copyright © 2017 Elsevier Inc. Terms and Conditions


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