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The 4-1BBζ costimulatory domain in chimeric antigen receptors enhances CD8+ T-cell functionality following T-cell receptor stimulation

Cancer Cell Int. 2023-12; 
Gerard J Chu, Charles G Bailey, Rajini Nagarajah, Sharon M Sagnella, Stephen Adelstein, John E J Rasko
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Proteins, Expression, Isolation and Analysis … 0.05 µg/mL biotinylated Protein L (#M00097, Genscript) for 60 min on ice, followed by two … reduced resolution compared to protein L detection due to endogenous CD3ζ expression. … Get A Quote

摘要

background: Chimeric antigen receptor (CAR) T-cells have revolutionized the treatment of CD19- and B-cell maturation antigen-positive haematological malignancies. However, the effect of a CAR construct on the function of T-cells stimulated via their endogenous T-cell receptors (TCRs) has yet to be comprehensively investigated. methods: Experiments were performed to systematically assess TCR signalling and function in CAR T-cells using anti-mesothelin human CAR T-cells as a model system. CAR T-cells expressing the CD28 or 4-1BB costimulatory endodomains were manufactured and compared to both untransduced T-cells and CAR T-cells with a non-functional endodomain. These cell products were treated with staphylococca... More

关键词

4-1BB, CAR, CD28, Cancer, Function, Immunology, Immunotherapy, Signaling