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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Clin+Cancer+Res
2016 ; 22
(7
): 1559-64
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Molecular Pathways: Breaking the Epithelial Cancer Barrier for Chimeric Antigen
Receptor and T-cell Receptor Gene Therapy
#MMPMID27037253
Hinrichs CS
Clin Cancer Res
2016[Apr]; 22
(7
): 1559-64
PMID27037253
show ga
Adoptive transfer of T cells genetically engineered to express a tumor-targeting
chimeric antigen receptor (CAR) or T-cell receptor (TCR) can mediate cancer
regression in some patients. CARs are synthetic single-chain proteins that use
antibody domains to target cell surface antigens. TCRs are natural heterodimeric
proteins that can target intracellular antigens through recognition of peptides
bound to human leukocyte antigens. CARs have shown promise in B-cell malignancies
and TCRs in melanoma, but neither approach has achieved clear success in an
epithelial cancer. Treatment of epithelial cancers may be particularly
challenging because of a paucity of target antigens expressed by carcinomas and
not by important healthy tissues. In addition, epithelial cancers may be
protected by inhibitory ligands and soluble factors in the tumor
microenvironment. One strategy to overcome these negative regulators is to
modulate expression of T-cell genes to enhance intrinsic T-cell function.
Programmable nucleases, which can suppress inhibitory genes, and inducible gene
expression systems, which can enhance stimulatory genes, are entering clinical
testing. Other work is delineating whether control of genes for immune checkpoint
receptors (e.g.,PDCD1, CTLA4) and cytokine and TCR signaling regulators
(e.g.,CBLB, CISH, IL12, IL15) can increase the antitumor activity of therapeutic
T cells.
|*Signal Transduction
[MESH]
|Animals
[MESH]
|Antibodies, Monoclonal/pharmacology/therapeutic use
[MESH]