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发帖数: 130 | 1 Hum Gene Ther Methods. 2016 Nov 29.
A RAPID CELL EXPANSION PROCESS FOR PRODUCTION OF ENGINEERED AUTOLOGOUS CAR-T
CELL THERAPIES.
Lu TL1, Pugach O2, Somerville RP3, Rosenberg SA4, Kochenderfer JN5, Better
M6, Feldman SA7.
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 trials1-6
sup>. The anti-CD19 CAR T cell production method used to support initial
trials relied on numerous manual, open process steps, cell culture media
supplemented with 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 NCI production process by removing human serum from the process to
minimize risk of viral contamination, moving process steps from an open
system to closed system operations to minimize the risk of microbial
contamination, and standardizing additional process steps to maximize
process consistency. In this study, we report a procedure for generating
CD19 CAR-T cells in 6 days, using a predominantly 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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