Pre-clinical development of Chimeric Antigen Receptor T-cell immunotherapy: implications of design for efficacy and safety

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Abstract

Following the landmark approvals by the United States Food and Drug Administration, the adoptive transfer of CD19-directed chimeric antigen receptor (CAR) T-cells has now entered mainstream clinical practice for patients with chemotherapy-resistant or refractory B-cell malignancies. These approvals have followed on from a prolonged period of pre-clinical evaluation, informing the design of clinical trials that have demonstrated unprecedented efficacy in this difficult to treat patient population. However, the delivery of autologous CAR-engineered T-cell therapy is complex, costly and not without significant risk. Here we summarize the key themes of CAR T-cell preclinical development and highlight a number of innovative strategies designed to further address toxicity and improve efficacy. In concert with the emerging promise of precision genome editing, it is hoped these next generation products will increase the repertoire of clinical applications of CAR T-cell therapy in malignant and perhaps other disease settings.
Original languageEnglish
JournalBaillieres Best Practice & Research in Clinical Haematology
Early online date21 Apr 2018
DOIs
Publication statusE-pub ahead of print - 21 Apr 2018

Keywords

  • Adoptive cell therapy
  • chimeric antigen receptor
  • engineering
  • cancer immunotherapy

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