CD137 (4-1BB) Engagement Fine-Tunes Synergistic IL-15- and IL-21-Driven NK Cell Proliferation.

To understand and dissect the mechanisms driving human NK cell proliferation, we exploited the methodology used in cell therapy to numerically expand NK cells in the presence of K562-derived artificial APC (aAPCs) and cytokines. For four consecutive weeks, high expression of CD137L by a K562-derived aAPC cell line could sustain NK cell expansion by 3 × 10-fold, whereas low expression of CD137L by the parental K562 cell line only supported the expansion by 2 × 10-fold. The level of expression of CD137L, however, did not modulate the sensitivity of K562 cells to the intrinsic cytotoxicity of NK cells.

A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy.

Vps34 is a phosphoinositide 3-kinase (PI3K) class III isoform that has attracted major attention over the recent years because of its role in autophagy. Herein we describe the biological characterization of SAR405, which is a low-molecular-mass kinase inhibitor of Vps34 (KD 1.5 nM).