The promise and potential pitfalls of chimeric antigen receptors Journal Article

Authors: Sadelain, M.; Brentjens, R.; Riviere, I.
Article Title: The promise and potential pitfalls of chimeric antigen receptors
Abstract: One important purpose of T cell engineering is to generate tumor-targeted T cells through the genetic transfer of antigen-specific receptors, which consist of either physiological, MHC-restricted T cell receptors (TCRs) or non MHC-restricted chimeric antigen receptors (CARs). CARs combine antigen-specificity and T cell activating properties in a single fusion molecule. First generation CARs, which included as their signaling domain the cytoplasmic region of the CD3ζ or Fc receptor γ chain, effectively redirected T cell cytotoxicity but failed to enable T cell proliferation and survival upon repeated antigen exposure. Receptors encompassing both CD28 and CD3ζ are the prototypes for second generation CARs, which are now rapidly expanding to a diverse array of receptors with different functional properties. First generation CARs have been tested in phase I clinical studies in patients with ovarian cancer, renal cancer, lymphoma, and neuroblastoma, where they have induced modest responses. Second generation CARs, which are just now entering the clinical arena in the B cell malignancies and other cancers, will provide a more significant test for this approach. If the immunogenicity of CARs can be averted, the versatility of their design and HLA-independent antigen recognition will make CARs tools of choice for T cell engineering for the development of targeted cancer immunotherapies. © 2009 Elsevier Ltd. All rights reserved.
Keywords: unclassified drug; clinical trial; review; nonhuman; neoplasms; lymphocyte proliferation; antigens, cd3; t-lymphocytes; animals; cell survival; cancer immunotherapy; mantle cell lymphoma; ovary cancer; carcinoembryonic antigen; epidermal growth factor receptor 2; cd20 antigen; recombinant fusion proteins; genetic engineering; antigen specificity; receptors, antigen, t-cell; neuroblastoma; melanoma antigen 1; immunogenicity; antigen recognition; drug response; lymphoma; gene therapy; chimeric antigen receptor; mucin 1; kidney cancer; epidermal growth factor receptor 3; chronic lymphatic leukemia; follicular lymphoma; immunotherapy, adoptive; t lymphocyte activation; cd19 antigen; lymphocyte antigen receptor; single chain fragment variable antibody; antigens, cd28; cd33 antigen; cd30 antigen; epidermal growth factor receptor 4; cd22 antigen; cd44v antigen; chimeric protein; cholinergic receptor; folate receptor alpha; interleukin 13 receptor alpha2; le(y) antigen; natural killer cell receptor nkg2d; oncofetal antigen; cell mediated cytotoxicity; major histocompatibility complex restriction
Journal Title: Current Opinion in Immunology
Volume: 21
Issue: 2
ISSN: 0952-7915
Publisher: Elsevier Inc.  
Date Published: 2009-04-01
Start Page: 215
End Page: 223
Language: English
DOI: 10.1016/j.coi.2009.02.009
PUBMED: 19327974
PROVIDER: scopus
PMCID: PMC5548385
Notes: --- - "Cited By (since 1996): 38" - "Export Date: 30 November 2010" - "CODEN: COPIE" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Renier J Brentjens
    195 Brentjens
  2. Michel W J Sadelain
    456 Sadelain
  3. Isabelle C Riviere
    164 Riviere