Research ArticleImmunotherapy

Rational development and characterization of humanized anti–EGFR variant III chimeric antigen receptor T cells for glioblastoma

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Science Translational Medicine  18 Feb 2015:
Vol. 7, Issue 275, pp. 275ra22
DOI: 10.1126/scitranslmed.aaa4963

CAR T cells drive glioblastoma therapy

Immunotherapy with chimeric antigen receptor (CAR) T cells can successfully treat B cell malignancies, but expansion into solid tumors has been limited by the lack of availability of tumor-specific antigens. Now, Johnson et al. target CAR T cells to a variant III mutation of the epidermal growth factor receptor (EGFRvIII), which is thought to be enriched in glioblastoma stem cells. They found that a low-affinity single-chain variable fragment was specific for EGFRvIII over wild-type EGFR and that CAR T cells transduced with this fragment were able to target antigen-expressing cells in vitro and in vivo in multiple mouse xenograft models of human glioblastoma. These cells are currently being moved into the clinic in a phase 1 clinical trial.

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