There has been dramatic success in treating patients with adoptive transfer of autologous
T cells genetically modified to express a chimeric antigen receptor redirecting them
to the antigen CD19. Despite this success, the application of chimeric antigen receptor
T-cell therapy in solid malignancies has encountered many challenges that need to
be overcome if similar success across other cancers is to become a reality. These
challenges can be classified into 6 categories: the heterogeneity of tumor cell clones
and tumor-associated antigen expression; poor T-cell trafficking into the tumor site;
poor T-cell survival and persistence; the presence of suppressive immune cells; the
secretion of suppressive soluble factors in the tumor microenvironment; and the upregulation
of T-cell intrinsic inhibitory pathways. We outline specific representative hurdles
in each of these categories and summarize the progress made in understanding them
and developing strategies to overcome them.
Abbreviations:
AICD (activation-induced cell death), AMP (adenosine monophosphate), APC (antigen-presenting cells), ATP (adenosine triphosphate), CAFs (cancer-associated fibroblasts), CAR (chimeric antigen receptor), CEA (carcinoembryonic antigen), CTLA4 (cytotoxic T-lymphocyte antigen 4), DAG (diacylglycerol), DGK (diacylglycerol kinase), HIF (hypoxia-inducible factor), IDO (indolamine-2,3-dioxygenase), IRs (inhibitor receptors), MDSCs (myeloid-derived suppressor cells), NKTs (natural killer T cells), PD-1 (programmed death receptor 1), PGE2 (prostaglandin E2), SCID (severe combined immunodeficiency), TAAs (tumor-associated antigens), TAMs (tumor-associated macrophages), TANs (tumor-associated neutrophils), TCR (T-cell receptor), TGF-β (transforming growth factor β), TILs (tumor-infiltrating lymphocytes), TME (tumor microenvironment), Tregs (regulatory T cells), TRUCK (T-cell redirected universal cytokine killing), TSA (tumor-specific antigen), VEGF (vascular endothelial growth factor)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: June 09, 2017
Accepted:
May 30,
2017
Received in revised form:
May 4,
2017
Received:
March 11,
2017
Identification
Copyright
© 2017 Elsevier Inc. All rights reserved.
