Preclinical characterization of DUOC-01, a cell therapy product derived from banked umbilical cord blood for use as an adjuvant to umbilical cord blood transplantation for treatment of inherited metabolic diseases.

Kurtzberg, Joanne; Buntz, Susan; Gentry, Tracy; Noeldner, Pamela; Ozamiz, April; Rusche, Benjamin; Storms, Robert W; Wollish, Amy; Wenger, David A; Balber, Andrew E

Preclinical characterization of DUOC-01, a cell therapy product derived from banked umbilical cord blood for use as an adjuvant to umbilical cord blood transplantation for treatment of inherited metabolic diseases.

dc.contributor.author	Kurtzberg, Joanne
dc.contributor.author	Buntz, Susan
dc.contributor.author	Gentry, Tracy
dc.contributor.author	Noeldner, Pamela
dc.contributor.author	Ozamiz, April
dc.contributor.author	Rusche, Benjamin
dc.contributor.author	Storms, Robert W
dc.contributor.author	Wollish, Amy
dc.contributor.author	Wenger, David A
dc.contributor.author	Balber, Andrew E
dc.date.accessioned	2022-03-23T19:39:30Z
dc.date.available	2022-03-23T19:39:30Z
dc.date.issued	2015-06
dc.date.updated	2022-03-23T19:39:30Z
dc.description.abstract	Background aims Cord blood (CB) transplantation slows neurodegeneration during certain inherited metabolic diseases. However, the number of donor cells in the brain of patients does not appear to be sufficient to provide benefit until several months after transplant. We developed the cell product DUOC-01 to provide therapeutic effects in the early post-transplant period. Methods DUOC-01 cultures initiated from banked CB units were characterized by use of time-lapse photomicroscopy during the 21-day manufacturing process. Antigen expression was measured by means of flow cytometry and immunocytochemistry; transcripts for cytokines and enzymes by quantitative real-time polymerase chain reaction; activities of lysosomal enzymes by direct biochemical analysis; alloreactivity of DUOC-01 and of peripheral blood (PB) mononuclear cells (MNC) to DUOC-01 by mixed lymphocyte culture methods; and cytokine secretion by Bioplex assays. Results DUOC-01 cultures contained highly active, attached, motile, slowly proliferating cells that expressed common (cluster of differentiation [CD]11b, CD14 and Iba1), M1 type (CD16, inducible nitric oxide synthase), and M2-type (CD163, CD206) macrophage or microglia markers. Activities of 11 disease-relevant lysosomal enzymes in DUOC-01 products were similar to those of normal PB cells. All DUOC-01 products secreted interleukin (IL)-6 and IL-10. Accumulation of transforming growth factor-β, IL-1β, interferon-γ and TNF-α in supernatants was variable. IL-12, IL-2, IL-4, IL-5 and IL-13 were not detected at significant concentrations. Galactocerebrosidase, transforming growth factor-β and IL-10 transcripts were specifically enriched in DUOC-01 relative to CB cells. PB MNCs proliferated and released cytokines in response to DUOC-01. DUOC-01 did not proliferate in response to mismatched MNC. Conclusions DUOC-01 has potential as an adjunctive cell therapy to myeloablative CB transplant for treatment of inherited metabolic diseases.
dc.identifier	S1465-3249(15)00070-5
dc.identifier.issn	1465-3249
dc.identifier.issn	1477-2566
dc.identifier.uri	https://hdl.handle.net/10161/24663
dc.language	eng
dc.publisher	Elsevier Inc.
dc.relation.ispartof	Cytotherapy
dc.relation.isversionof	10.1016/j.jcyt.2015.02.006
dc.subject	Cells, Cultured
dc.subject	Lysosomes
dc.subject	Fetal Blood
dc.subject	Animals
dc.subject	Humans
dc.subject	Mice
dc.subject	Metabolic Diseases
dc.subject	Inflammation
dc.subject	Adjuvants, Immunologic
dc.subject	Cytokines
dc.subject	Cord Blood Stem Cell Transplantation
dc.subject	Flow Cytometry
dc.subject	Cell Differentiation
dc.subject	Cell Proliferation
dc.subject	Cell Shape
dc.subject	Cell- and Tissue-Based Therapy
dc.title	Preclinical characterization of DUOC-01, a cell therapy product derived from banked umbilical cord blood for use as an adjuvant to umbilical cord blood transplantation for treatment of inherited metabolic diseases.
dc.type	Journal article
duke.contributor.orcid	Kurtzberg, Joanne\|0000-0002-3370-0703
pubs.begin-page	803
pubs.end-page	815
pubs.issue	6
pubs.organisational-group	Duke
pubs.organisational-group	School of Medicine
pubs.organisational-group	Staff
pubs.organisational-group	Clinical Science Departments
pubs.organisational-group	Institutes and Centers
pubs.organisational-group	Pathology
pubs.organisational-group	Pediatrics
pubs.organisational-group	Duke Cancer Institute
pubs.organisational-group	Institutes and Provost's Academic Units
pubs.organisational-group	Initiatives
pubs.organisational-group	Duke Innovation & Entrepreneurship
pubs.organisational-group	Pediatrics, Transplant and Cellular Therapy
pubs.publication-status	Published
pubs.volume	17