Definition and application of good manufacturing process-compliant production of CEA-specific chimeric antigen receptor expressing T-cells for phase I/II clinical trial.
Authors
Guest, RKirillova, N
Mowbray, S
Gornall, Hannah
Rothwell, Dominic G
Cheadle, Eleanor J
Austin, E
Smith, K
Watt, S
Kühlcke, K
Westwood, N
Thistlethwaite, Fiona C
Hawkins, Robert E
Gilham, David E
Affiliation
Cellular Therapeutics, Grafton Street, ManchesterIssue Date
2014-02
Metadata
Show full item recordAbstract
Adoptive cell therapy employing gene-modified T-cells expressing chimeric antigen receptors (CARs) has shown promising preclinical activity in a range of model systems and is now being tested in the clinical setting. The manufacture of CAR T-cells requires compliance with national and European regulations for the production of medicinal products. We established such a compliant process to produce T-cells armed with a first-generation CAR specific for carcinoembryonic antigen (CEA). CAR T-cells were successfully generated for 14 patients with advanced CEA(+) malignancy. Of note, in the majority of patients, the defined procedure generated predominantly CD4(+) CAR T-cells with the general T-cell population bearing an effector-memory phenotype and high in vitro effector function. Thus, improving the process to generate less-differentiated T-cells would be more desirable in the future for effective adoptive gene-modified T-cell therapy. However, these results confirm that CAR T-cells can be generated in a manner compliant with regulations governing medicinal products in the European Union.Citation
Definition and application of good manufacturing process-compliant production of CEA-specific chimeric antigen receptor expressing T-cells for phase I/II clinical trial. 2014, 63 (2):133-45 Cancer Immunol ImmunotherJournal
Cancer Immunology, ImmunotherapyDOI
10.1007/s00262-013-1492-9PubMed ID
24190544Type
ArticleLanguage
enISSN
1432-0851ae974a485f413a2113503eed53cd6c53
10.1007/s00262-013-1492-9
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