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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. © 2013 Springer-Verlag Berlin Heidelberg.

Original publication

DOI

10.1007/s00262-013-1492-9

Type

Journal article

Journal

Cancer Immunology, Immunotherapy

Publication Date

2013

Pages

1 - 13