Clinical development of CAR T cells-challenges and opportunities in translating innovative treatment concepts

EMBO Mol Med. 2017 Sep;9(9):1183-1197. doi: 10.15252/emmm.201607485.


Chimeric antigen receptor (CAR) T cell therapy, together with checkpoint inhibition, has been celebrated as a breakthrough technology due to the substantial benefit observed in clinical trials with patients suffering from relapsed or refractory B-cell malignancies. In this review, we provide a comprehensive overview of the clinical trials performed so far worldwide and analyze parameters such as targeted antigen and indication, CAR molecular design, CAR T cell manufacturing, anti-tumor activities, and related toxicities. More than 200 CAR T cell clinical trials have been initiated so far, most of which aim to treat lymphoma or leukemia patients using CD19-specific CARs. An increasing number of studies address solid tumors as well. Notably, not all clinical trials conducted so far have shown promising results. Indeed, in a few patients CAR T cell therapy resulted in severe adverse events with fatal outcome. Of note, less than 10% of the ongoing CAR T cell clinical trials are performed in Europe. Taking lead from our analysis, we discuss the problems and general hurdles preventing efficient clinical development of CAR T cells as well as opportunities, with a special focus on the European stage.

Keywords: ATMPs; cancer; immunotherapy; regulatory issues; toxicities.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Clinical Trials as Topic
  • Humans
  • Immunotherapy*
  • Leukemia / immunology
  • Leukemia / therapy*
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / therapy*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation*


  • Receptors, Antigen, T-Cell