Chimeric antigen receptor therapy for cancer

David M. Barrett, Nathan Singh, David L. Porter, Stephan A. Grupp, Carl H. June

Research output: Contribution to journalReview articlepeer-review

262 Scopus citations

Abstract

Improved outcomes for patients with cancer hinge on the development of new targeted therapies with acceptable short-term and long-term toxicity. Progress in basic, preclinical, and clinical arenas spanning cellular immunology, synthetic biology, and cell-processing technologies has paved the way for clinical applications of chimeric antigen receptor-based therapies. This new form of targeted immunotherapy merges the exquisite targeting specificity of monoclonal antibodies with the potent cytotoxicity and long-term persistence provided by cytotoxic T cells. Although this field is still in its infancy, clinical trials have already shown clinically significant antitumor activity in neuroblastoma, chronic lymphocytic leukemia, and B cell lymphoma, and trials targeting a variety of other adult and pediatric malignancies are under way. Ongoing work is focused on identifying optimal tumor targets and on elucidating and manipulating both cell- and host-associated factors to support expansion and persistence of the genetically engineered cells in vivo. The potential to target essentially any tumor-associated cell-surface antigen for which a monoclonal antibody can be made opens up an entirely new arena for targeted therapy of cancer.

Original languageEnglish
Pages (from-to)333-347
Number of pages15
JournalAnnual review of medicine
Volume65
DOIs
StatePublished - Jan 2014

Keywords

  • Adoptive transfer
  • Chimeric antigen receptor
  • Gene transfer
  • Synthetic biology
  • T cell receptor

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