{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T06:07:26Z","timestamp":1792822046524,"version":"4.5.0"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>CD38 is highly expressed on immune cells. It catabolizes NAD+, which is a critical cofactor for enzymes involved in metabolism and energy production. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>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. <\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1640611","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T10:42:58Z","timestamp":1760352178000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Inhibition of CD38 enzyme activity on engrafted human immune cells enhances NAD+ metabolism and inhibits inflammation in an in-vivo model of 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