The basic principles of chimeric antigen receptor design Journal Article


Authors: Sadelain, M.; Brentjens, R.; Riviere, I.
Article Title: The basic principles of chimeric antigen receptor design
Abstract: Chimeric antigen receptors (CAR) are recombinant receptors that provide both antigen-binding and T-cell-activating functions. A multitude of CARs has been reported over the past decade, targeting an array of cell surface tumor antigens. Their biologic functions have dramatically changed following the introduction of tripartite receptors comprising a costimulatory domain, termed second-generation CARs. These have recently shown clinical benefit in patients treated with CD19-targeted autologous T cells. CARs may be combined with costimulatory ligands, chimeric costimulatory receptors, or cytokines to further enhance T-cell potency, specificity, and safety. CARs represent a new class of drugs with exciting potential for cancer immunotherapy. Significance: CARs are a new class of drugs with great potential for cancer immunotherapy. Upon their expression in T lymphocytes, CARs direct potent, targeted immune responses that have recently shown encouraging clinical outcomes in a subset of patients with B-cell malignancies. This review focuses on the design of CARs, including the requirements for optimal antigen recognition and different modalities to provide costimulatory support to targeted T cells, which include the use of second- and thirdgeneration CARs, costimulatory ligands, chimeric costimulatory receptors, and cytokines. © 2013 American Association for Cancer Research.
Keywords: signal transduction; protein expression; review; nonhuman; solid tumor; neoplasms; cd3 antigen; cell proliferation; t lymphocyte; t-lymphocytes; animals; interleukin 2; unindexed drug; cancer immunotherapy; carcinoembryonic antigen; epidermal growth factor receptor; epidermal growth factor receptor 2; cytotoxicity; cell lineage; cell specificity; genetic transduction; cd20 antigen; cytokine; prostate specific membrane antigen; immune response; recombinant fusion proteins; melanoma antigen 1; ny eso 1 antigen; cell therapy; melanoma antigen; tumor necrosis factor receptor; ephrin receptor a2; mucin 1; immunoglobulin kappa chain; cd24 antigen; immunotherapy, adoptive; prostate stem cell antigen; cd19 antigen; lymphocyte antigen receptor; receptors, antigen; epstein barr virus; cd38 antigen; cd33 antigen; mesothelin; nerve cell adhesion molecule l1; cd30 antigen; hla system; cd22 antigen; natural killer cell receptor nkg2d; oncofetal antigen; oncogene neu; folate receptor 1; cd23 antigen; cell engineering
Journal Title: Cancer Discovery
Volume: 3
Issue: 4
ISSN: 2159-8274
Publisher: American Association for Cancer Research  
Date Published: 2013-04-01
Start Page: 388
End Page: 398
Language: English
DOI: 10.1158/2159-8290.cd-12-0548
PROVIDER: scopus
PMCID: PMC3667586
PUBMED: 23550147
DOI/URL:
Notes: --- - "Export Date: 3 June 2013" - "Source: Scopus"
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MSK Authors
  1. Renier J Brentjens
    198 Brentjens
  2. Michel W J Sadelain
    462 Sadelain
  3. Isabelle C Riviere
    168 Riviere