GEO series

Structural design of engineered costimulation determines tumor rejection kinetics and persistence of CAR T cells

GSE68329 Homo sapiens Expression profiling by array 24 samples Submitted 2016/04/19 Platform GPL10558

Summary

The choice of costimulatory domain in CAR design dictates the kinetics of in vivo anti-tumor responses, affecting potency, quality and durability. We show that 1928z results in more vigorous effector functions, whereas 19BBz design compensates for their lesser cytotoxic potency by steadily building up their numbers. Therapeutic function can be further improved by combining CD28 and 4-1BB costimulation. 1928z-41BBL was revealed to provide optimal combined costimulation, exhibiting highly therapeutic efficiency with balanced T cell effector function and accumulation. Endogenous IFN-β/IRF7 pathway activation was found in 1928z-41BBL T cell and is required for effector function acquisition. The role of the IFN-β/IRF7 pathway provides a novel mechanism through which engineering T cells improve therapeutic effect by self-providing ‘signal 3’.

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Direct links to NCBI, no account and no request form: the whole study as GSE68329_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 24 samples.

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Also filed as BioProject PRJNA282453. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 26461090) ↗

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