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2016 ; 28
(7
): 355-63
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Chimeric antigen receptor-modified T cells strike back
#MMPMID27021308
Frigault MJ
; Maus MV
Int Immunol
2016[Jul]; 28
(7
): 355-63
PMID27021308
show ga
Chimeric antigen receptors (CARs) are engineered molecules designed to endow a
polyclonal T-cell population with the ability to recognize tumor-associated
surface antigens. In their simplest form, CARs comprise a targeting moiety in the
form of a single-chain variable fragment from an antibody connected to various
intracellular signaling domains allowing for T-cell activation. This powerful
approach combines the specificity of an antibody with the cytotoxic ability of a
T cell. There has been much excitement since early phase trials of CAR-T cells
targeting CD19 expressed on B-cell malignancies demonstrated remarkable efficacy
in inducing long-term, stable remissions in otherwise relapsed/refractory
disease. Despite these successes, we have just begun to understand the
intricacies of CAR biology with efforts underway to utilize this platform in the
treatment of other, previously refractory malignancies. Challenges currently
include identification of viable cancer targets, management strategies for
potentially severe and irreversible toxicities and overcoming the
immunosuppressive nature of the tumor microenvironment. This review will focus on
basic CAR structure and function, previous success and new approaches aimed at
the broader application of CAR-T-cell therapy.
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