Abstract

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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Acknowledgements

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.).

Author information

Author notes

  1. These authors contributed equally: Ayesha Aijaz, Matthew Li, David Smith.

Affiliations

  1. Department of Biomedical Engineering, Rutgers University, Piscataway, NJ, USA

    • Ayesha Aijaz
    • , Ronke M. Olabisi
    •  & Biju Parekkadan
  2. Department of Surgery, Center for Surgery, Innovation, and Bioengineering, Massachusetts General Hospital, Harvard Medical School and Shriners Hospitals for Children, Boston, MA, USA

    • Matthew Li
    • , Danika Khong
    •  & Biju Parekkadan
  3. Hitachi Chemical Advanced Therapeutics Solutions, Allendale, NJ, USA

    • David Smith
    • , Courtney LeBlon
    •  & Robert Preti
  4. Department of Chemical Engineering, Institute for Medical Engineering and Science, Division of Health Science and Technology, and the David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA

    • Owen S. Fenton
    •  & Daniel G. Anderson
  5. Cancer Institute of New Jersey, New Brunswick, NJ, USA

    • Steven Libutti
  6. Human Genetics Institute of New Jersey, RUCDR, Piscataway, NJ, USA

    • Jay Tischfield
  7. Cellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA

    • Marcela V. Maus
  8. BlueRock Therapeutics, Cambridge, MA, USA

    • Robert Deans
  9. Sentien Biotechnologies, Inc, Lexington, MA, USA

    • Rita N. Barcia
    •  & Biju Parekkadan
  10. Cell Manipulation Core Facility, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    • Jerome Ritz
  11. Harvard Stem Cell Institute, Cambridge, MA, USA

    • Jerome Ritz
    •  & Biju Parekkadan

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Contributions

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.

Competing interests

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.

Corresponding author

Correspondence to Biju Parekkadan.

Supplementary information

  1. Supplementary Information

    Supplementary tables and references

  2. Supplementary Data

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

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DOI

https://doi.org/10.1038/s41551-018-0246-6

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