Definition and application of good manufacturing process-compliant production of CEA-specific chimeric antigen receptor expressing T-cells for phase I/II clinical trial

Cancer Immunol Immunother. 2014 Feb;63(2):133-45. doi: 10.1007/s00262-013-1492-9. Epub 2013 Nov 5.


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.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer*
  • Carcinoembryonic Antigen / immunology*
  • Chimerin Proteins / biosynthesis*
  • Humans
  • Immunophenotyping
  • Interferon-gamma / biosynthesis
  • Receptors, Antigen, T-Cell / biosynthesis*
  • T-Lymphocytes / immunology*


  • Carcinoembryonic Antigen
  • Chimerin Proteins
  • Receptors, Antigen, T-Cell
  • Interferon-gamma