CAR-T Cells Inflict Sequential Killing of Multiple Tumor Target Cells
Alexander J Davenport, Misty R Jenkins, Ryan S Cross, Carmen S Yong, H Miles Prince, David S Ritchie, Joseph A Trapani, Michael H Kershaw, Phillip K Darcy, Paul J Neeson
CANCER IMMUNOLOGY RESEARCH | AMER ASSOC CANCER RESEARCH | Published : 2015
Adoptive therapy with chimeric antigen receptor (CAR) T cells shows great promise clinically. However, there are important aspects of CAR-T-cell biology that have not been explored, particularly with respect to the kinetics of activation, immune synapse formation, and tumor cell killing. Moreover, the effects of signaling via the endogenous T-cell receptor (TCR) or CAR on killing kinetics are unclear. To address these issues, we developed a novel transgenic mouse (designated CAR.OT-I), in which CD8(+) T cells coexpressed the clonogenic OT-I TCR, recognizing the H-2K(b)-presented ovalbumin peptide SIINFEKL, and an scFv specific for human HER2. Primed CAR.OT-I T cells were mixed with SIINFEKL-..View full abstract
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Awarded by NHMRC Senior Research Fellowships
This work was funded by a program grant from the National Health and Medical Research Council (NHMRC). A.J. Davenport was supported by a scholarship from the Fight Cancer Foundation, and M.R. Jenkins is supported by a National Health and Medical Research Council of Australia (NHMRC)/RG Menzies postdoctoral training fellowship and an NHMRC New Investigator Project grant. P.K. Darcy and M.H. Kershaw were supported by NHMRC Senior Research Fellowships (#1041828 and 1058388, respectively).