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Adv Drug Deliv Rev. 2017 May 15;114:222-239. doi: 10.1016/j.addr.2017.06.005. Epub 2017 Jun 15.

Cells as advanced therapeutics: State-of-the-art, challenges, and opportunities in large scale biomanufacturing of high-quality cells for adoptive immunotherapies.

Author information

1
The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Atlanta, GA 30332-0313, United States; The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332, United States. Electronic address: ndwarshuis3@gatech.edu.
2
The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332, United States; Department of Material Science and Engineering, Georgia Institute of Technology, Atlanta, GA 30332, United States. Electronic address: kparratt4@gatech.edu.
3
The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Atlanta, GA 30332-0313, United States; The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332, United States. Electronic address: ansm3@gatech.edu.
4
The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Atlanta, GA 30332-0313, United States; The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332, United States. Electronic address: krishnendu.roy@bme.gatech.edu.

Abstract

Therapeutic cells hold tremendous promise in treating currently incurable, chronic diseases since they perform multiple, integrated, complex functions in vivo compared to traditional small-molecule drugs or biologics. However, they also pose significant challenges as therapeutic products because (a) their complex mechanisms of actions are difficult to understand and (b) low-cost bioprocesses for large-scale, reproducible manufacturing of cells have yet to be developed. Immunotherapies using T cells and dendritic cells (DCs) have already shown great promise in treating several types of cancers, and human mesenchymal stromal cells (hMSCs) are now extensively being evaluated in clinical trials as immune-modulatory cells. Despite these exciting developments, the full potential of cell-based therapeutics cannot be realized unless new engineering technologies enable cost-effective, consistent manufacturing of high-quality therapeutic cells at large-scale. Here we review cell-based immunotherapy concepts focused on the state-of-the-art in manufacturing processes including cell sourcing, isolation, expansion, modification, quality control (QC), and culture media requirements. We also offer insights into how current technologies could be significantly improved and augmented by new technologies, and how disciplines must converge to meet the long-term needs for large-scale production of cell-based immunotherapies.

KEYWORDS:

Adoptive cell therapy; Bioreactor; Chimeric antigen receptor; Dendritic cells; Immunotherapy; Mesenchymal stromal cells; T cells; Tumor infiltrating lymphocytes

PMID:
28625827
DOI:
10.1016/j.addr.2017.06.005
[Indexed for MEDLINE]

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