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CARbodies: Human Antibodies Against Cell Surface Tumor Antigens Selected From
Repertoires Displayed on T Cell Chimeric Antigen Receptors
#MMPMID23695536
Alonso-Camino V
; Sánchez-Martín D
; Compte M
; Nuñez-Prado N
; Diaz RM
; Vile R
; Alvarez-Vallina L
Mol Ther Nucleic Acids
2013[May]; 2
(5
): e93
PMID23695536
show ga
A human single-chain variable fragment (scFv) antibody library was expressed on
the surface of human T cells after transduction with lentiviral vectors (LVs).
The repertoire was fused to a first-generation T cell receptor ? (TCR?)-based
chimeric antigen receptor (CAR). We used this library to isolate antibodies
termed CARbodies that recognize antigens expressed on the tumor cell surface in a
proof-of-principle system. After three rounds of activation-selection there was a
clear repertoire restriction, with the emergence dominant clones. The CARbodies
were purified from bacterial cultures as soluble and active proteins.
Furthermore, to validate its potential application for adoptive cell therapy,
human T cells were transduced with a LV encoding a second-generation
costimulatory CAR (CAR(v2)) bearing the selected CARbodies. Transduced human
primary T cells expressed significant levels of the CARbodies-based CAR(v2)
fusion protein on the cell surface, and importantly could be specifically
activated, after stimulation with tumor cells. This approach is a promising tool
for the generation of antibodies fully adapted to the display format (CAR) and
the selection context (cell synapse), which could extend the scope of current
adoptive cell therapy strategies with CAR-redirected T cells.Molecular
Therapy-Nucleic Acids (2013) 2, e93; doi:10.1038/mtna.2013.19; published online
21 May 2013.
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