Journal
EMBO MOLECULAR MEDICINE
Volume 9, Issue 9, Pages 1183-1197Publisher
WILEY
DOI: 10.15252/emmm.201607485
Keywords
ATMPs; cancer; immunotherapy; regulatory issues; toxicities
Categories
Funding
- European Union [667980]
- LOEWE Center for Cell and Gene Therapy Frankfurt - Hessische Ministerium fur Wissenschaft und Kunst (HMWK) [III L 5-518/17.004]
- H2020 Societal Challenges Programme [667980] Funding Source: H2020 Societal Challenges Programme
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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.
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