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Published Online: 1 December 2016

A Rapid Cell Expansion Process for Production of Engineered Autologous CAR-T Cell Therapies

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Publication: Human Gene Therapy Methods
Volume 27, Issue Number 6

Abstract

The treatment of B-cell malignancies by adoptive cell transfer (ACT) of anti-CD19 chimeric antigen receptor T cells (CD19 CAR-T) has proven to be a highly successful therapeutic modality in several clinical trials.1–6 The anti-CD19 CAR-T cell production method used to support initial trials relied on numerous manual, open process steps, human serum, and 10 days of cell culture to achieve a clinical dose.7 This approach limited the ability to support large multicenter clinical trials, as well as scale up for commercial cell production. Therefore, studies were completed to streamline and optimize the original National Cancer Institute production process by removing human serum from the process in order to minimize the risk of viral contamination, moving process steps from an open system to functionally closed system operations in order to minimize the risk of microbial contamination, and standardizing additional process steps in order to maximize process consistency. This study reports a procedure for generating CD19 CAR-T cells in 6 days, using a functionally closed manufacturing process and defined, serum-free medium. This method is able to produce CD19 CAR-T cells that are phenotypically and functionally indistinguishable from cells produced for clinical trials by the previously described production process.

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Information & Authors

Information

Published In

cover image Human Gene Therapy Methods
Human Gene Therapy Methods
Volume 27Issue Number 6December 2016
Pages: 209 - 218
PubMed: 27897048

History

Published in print: December 2016
Published online: 1 December 2016
Published ahead of production: 29 November 2016
Accepted: 22 November 2016
Received: 5 August 2016

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    Authors

    Affiliations

    Tangying Lily Lu
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
    Omar Pugach
    ImaginAb, Inc., Inglewood, California
    KITE Pharma, Santa Monica, California.
    Robert Somerville
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
    Steven A. Rosenberg
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
    James N. Kochenderfer
    Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
    Marc Better
    KITE Pharma, Santa Monica, California.
    Steven A. Feldman* [email protected]
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

    Notes

    *
    Dr. Steven A. Feldman, Surgery Branch, National Cancer Institute, 10 Center Drive, MSC 1201, Bldg. 10, ACRF, 1B37A, Bethesda, MD 20892. E-mail: [email protected]

    Disclosure Statement

    M.B. has employment and equity ownership in Kite Pharma. O.P. is a former KITE Pharma employee with no outstanding financial interests. No competing financial interests exist for the remaining authors.

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