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Inhibition of CD38 enzyme activity on engrafted human immune cells enhances NAD+ metabolism and inhibits inflammation in an in-vivo model of xeno-GvHD
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Inhibition of CD38 enzyme activity on engrafted human immune cells enhances NAD+ metabolism and inhibits inflammation in an in-vivo model of xeno-GvHD
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Inhibition of CD38 enzyme activity on engrafted human immune cells enhances NAD+ metabolism and inhibits inflammation in an in-vivo model of xeno-GvHD
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Journal Article
Inhibition of CD38 enzyme activity on engrafted human immune cells enhances NAD+ metabolism and inhibits inflammation in an in-vivo model of xeno-GvHD
2025
Overview
CD38 is highly expressed on immune cells. It catabolizes NAD+, which is a critical cofactor for enzymes involved in metabolism and energy production.
We developed TNB-738, a fully human antibody that potently inhibits human CD38 enzymatic activity on human immune cells, resulting in a dose-dependent increase of intracellular NAD+ levels. TNB-738 does not show immune effector functions, does not induce direct cell killing of CD38 positive cells and is not internalized. In vivo, treatment with TNB-738 following infusion of human PBMCs into NSG mice resulted in significantly lower clinical scores, prolonged overall survival, less expansion of engrafted human CD45+ cells and a significant expansion of Tregs.
CD38 positive T cells regulate NAD+ metabolism in inflamed tissues and blockade of CD38 enzyme activity by TNB-738 could represent a novel class of therapeutics for the treatment of inflammatory conditions, including GvHD.
Publisher
Frontiers Media SA,Frontiers,Frontiers Media S.A
Subject
ADP-ribosyl Cyclase 1 - antagonists & inhibitors
/ ADP-ribosyl Cyclase 1 - immunology
/ ADP-ribosyl Cyclase 1 - metabolism
/ Animals
/ CD38
/ Enzymes
/ Graft vs Host Disease - drug therapy
/ Graft vs Host Disease - immunology
/ Graft vs Host Disease - metabolism
/ GvHD
/ Humans
/ Membrane Glycoproteins - antagonists & inhibitors
/ Membrane Glycoproteins - immunology
/ Membrane Glycoproteins - metabolism
/ Mice
/ NAD
/ Proteins
/ Reagents
/ Spleen
/ TNB-738
