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Trends Immunol. 2015 Aug;36(8):494-502. doi: 10.1016/j.it.2015.06.004. Epub 2015 Jul 11.

Engineering CAR-T cells: Design concepts.

Author information

1
Program in Immunology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Seattle, WA 98109, USA.
2
Program in Immunology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Seattle, WA 98109, USA. Electronic address: sriddell@fredhutch.org.

Abstract

Despite being empirically designed based on a simple understanding of TCR signaling, T cells engineered with chimeric antigen receptors (CARs) have been remarkably successful in treating patients with advanced refractory B cell malignancies. However, many challenges remain in improving the safety and efficacy of this therapy and extending it toward the treatment of epithelial cancers. Other aspects of TCR signaling beyond those directly provided by CD3ζ and CD28 phosphorylation strongly influence a T cell's ability to differentiate and acquire full effector functions. Here, we discuss how the principles of TCR recognition, including spatial constraints, Kon/Koff rates, and synapse formation, along with in-depth analysis of CAR signaling might be applied to develop safer and more effective synthetic tumor targeting receptors.

PMID:
26169254
PMCID:
PMC4746114
DOI:
10.1016/j.it.2015.06.004
[Indexed for MEDLINE]
Free PMC Article

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