A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells.

Abstract:

:An unmet need in cell engineering is the availability of a single transgene encoded, functionally inert, human polypeptide that can serve multiple purposes, including ex vivo cell selection, in vivo cell tracking, and as a target for in vivo cell ablation. Here we describe a truncated human EGFR polypeptide (huEGFRt) that is devoid of extracellular N-terminal ligand binding domains and intracellular receptor tyrosine kinase activity but retains the native amino acid sequence, type I transmembrane cell surface localization, and a conformationally intact binding epitope for pharmaceutical-grade anti-EGFR monoclonal antibody, cetuximab (Erbitux). After lentiviral transduction of human T cells with vectors that coordinately express tumor-specific chimeric antigen receptors and huEGFRt, we show that huEGFRt serves as a highly efficient selection epitope for chimeric antigen receptor(+) T cells using biotinylated cetuximab in conjunction with current good manufacturing practices (cGMP)-grade anti-biotin immunomagnetic microbeads. Moreover, huEGFRt provides a cell surface marker for in vivo tracking of adoptively transferred T cells using both flow cytometry and immunohistochemistry, and a target for cetuximab-mediated antibody-dependent cellular cytotoxicity and in vivo elimination. The versatility of huEGFRt and the availability of pharmaceutical-grade reagents for its clinical application denote huEGFRt as a significant new tool for cellular engineering.

journal_name

Blood

journal_title

Blood

authors

Wang X,Chang WC,Wong CW,Colcher D,Sherman M,Ostberg JR,Forman SJ,Riddell SR,Jensen MC

doi

10.1182/blood-2011-02-337360

subject

Has Abstract

pub_date

2011-08-04 00:00:00

pages

1255-63

issue

5

eissn

0006-4971

issn

1528-0020

pii

blood-2011-02-337360

journal_volume

118

pub_type

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