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Biomanufacturing for clinically advanced cell therapies


The achievements of cell-based therapeutics have galvanized efforts to bring cell therapies to the market. To address the demands of the clinical and eventual commercial-scale production of cells, and with the increasing generation of large clinical datasets from chimeric antigen receptor T-cell immunotherapy, from transplants of engineered haematopoietic stem cells and from other promising cell therapies, an emphasis on biomanufacturing requirements becomes necessary. Robust infrastructure should address current limitations in cell harvesting, expansion, manipulation, purification, preservation and formulation, ultimately leading to successful therapy administration to patients at an acceptable cost. In this Review, we highlight case examples of cutting-edge bioprocessing technologies that improve biomanufacturing efficiency for cell therapies approaching clinical use.

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Fig. 1: Cell-therapy pharmacoeconomics and manufacture.
Fig. 2: Process optimization for the expansion of cells and for cell collection from microcarriers.
Fig. 3: Towards high-throughput label-free purification.
Fig. 4: Streamlining the genetic modification of cells for therapy.
Fig. 5: Overview of current tools for differentiating PSCs into retinal and neuronal lineages.
Fig. 6: Islet encapsulation.
Fig. 7: Supply chain for CTPs.
Fig. 8: Segmented costs for translating cell therapeutics.


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We thank a number of colleagues for feedback on a draft of the manuscript, specifically B. Hampson and T. Heathman from Hitachi Chemical Advanced Therapeutics Solutions. This work was supported in part by the Shriners Hospitals for Children (B.P.) and by the National Institutes of Health Grant R01EB012521 (B.P.).

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All authors contributed to the writing of subsections of the manuscript. A.A., M.L., D.S., R.P. and B.P. contributed to all sections and to figure preparation. D.K., J.T. and R.D. contributed to the content relevant to iPSCs and ESCs. C.L. contributed to content on biopreservation. O.S.F., R.M.O. and D.G.A. contributed to the discussion of cell–material composites. S.L., M.V.M. and J.R. contributed to the cell-engineering discussion. R.N.B. contributed to the content on cell expansion.

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Correspondence to Biju Parekkadan.

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A.A., M.L., O.S.F., D.K., M.V.M., J.R., J.T., R.M.O. and S.L. declare no competing interests. D.S., C.L. and R.P. are employees of Hitachi Chemical Advanced Therapeutics Solutions. R.D. owns equity in BlueRock Therapeutics. D.G.A. is a founder and equity shareholder in Siglion Therapeutics. R.N.B. is an employee and equity shareholder of Sentien Biotechnologies, Inc. B.P. is a founder and equity shareholder of Sentien Biotechnologies, Inc.

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Phase-II and Phase-III clinical trials that include the use of cell therapies

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Aijaz, A., Li, M., Smith, D. et al. Biomanufacturing for clinically advanced cell therapies. Nat Biomed Eng 2, 362–376 (2018).

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