Format

Send to

Choose Destination
Curr Opin Immunol. 2009 Apr;21(2):215-23. doi: 10.1016/j.coi.2009.02.009. Epub 2009 Mar 25.

The promise and potential pitfalls of chimeric antigen receptors.

Author information

1
Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. m-sadelain@ski.mskcc.org

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 CD3zeta or Fc receptor gamma chain, effectively redirected T cell cytotoxicity but failed to enable T cell proliferation and survival upon repeated antigen exposure. Receptors encompassing both CD28 and CD3zeta 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.

PMID:
19327974
PMCID:
PMC5548385
DOI:
10.1016/j.coi.2009.02.009
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center