Journal
TRENDS IN IMMUNOLOGY
Volume 36, Issue 8, Pages 494-502Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.it.2015.06.004
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Funding
- NCI NIH HHS [R01 CA136551, R01 CA114536, P50 CA138293] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA136551, R01CA114536, P50CA138293] Funding Source: NIH RePORTER
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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 CD3 zeta 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.
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