Engineered dendritic cells from cord blood and adult blood accelerate effector T cell immune reconstitution against HCMV.

2.50
Hdl Handle:
http://hdl.handle.net/10033/556994
Title:
Engineered dendritic cells from cord blood and adult blood accelerate effector T cell immune reconstitution against HCMV.
Authors:
Daenthanasanmak, Anusara; Salguero, Gustavo; Sundarasetty, Bala Sai; Waskow, Claudia; Cosgun, Kadriye Nehir; Guzman, Carlos A; Riese, Peggy ( 0000-0001-6796-6780 ) ; Gerasch, Laura; Schneider, Andreas; Ingendoh, Alexandra; Messerle, Martin; Gabaev, Ildar; Woelk, Benno; Ruggiero, Eliana; Schmidt, Manfred; von Kalle, Christof; Figueiredo, Constanca; Eiz-Vesper, Britta; von Kaisenberg, Constantin; Ganser, Arnold; Stripecke, Renata
Abstract:
Human cytomegalovirus (HCMV) harmfully impacts survival after peripheral blood hematopoietic stem cell transplantation (PB-HSCT). Delayed immune reconstitution after cord blood (CB)-HSCT leads to even higher HCMV-related morbidity and mortality. Towards a feasible dendritic cell therapy to accelerate de novo immunity against HCMV, we validated a tricistronic integrase-defective lentiviral vector (coexpressing GM-CSF, IFN-α, and HCMV pp65 antigen) capable to directly induce self-differentiation of PB and CB monocytes into dendritic cells processing pp65 ("SmyleDCpp65"). In vitro, SmyleDCpp65 resisted HCMV infection, activated CD4(+) and CD8(+) T cells and expanded functional pp65-specific memory cytotoxic T lymphocytes (CTLs). CD34(+) cells obtained from PB and CB were transplanted into irradiated NOD.Rag1(-/-).IL2γc(-/-) mice. Donor-derived SmyleDCpp65 administration after PB-HSCT stimulated peripheral immune effects: lymph node remodeling, expansion of polyclonal effector memory CD8(+) T cells in blood, spleen and bone marrow, and pp65-reactive CTL and IgG responses. SmyleDCpp65 administration after CB-HSCT significantly stimulated thymopoiesis. Expanded frequencies of CD4(+)/CD8(+) T cell precursors containing increased levels of T-cell receptor excision circles in thymus correlated with peripheral expansion of effector memory CTL responses against pp65. The comparative in vivo modeling for PB and CB-HSCT provided dynamic and spatial information regarding human T and B cell reconstitution. In vivo potency supports future clinical development of SmyleDCpp65.
Affiliation:
Helmholtz Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany.
Citation:
Engineered dendritic cells from cord blood and adult blood accelerate effector T cell immune reconstitution against HCMV. 2015, 1:14060 Mol Ther Methods Clin Dev
Journal:
Molecular therapy. Methods & clinical development
Issue Date:
2015
URI:
http://hdl.handle.net/10033/556994
DOI:
10.1038/mtm.2014.60
PubMed ID:
26052526
Type:
Article
Language:
en
ISSN:
2329-0501
Appears in Collections:
publications of the research group vaccinology and applied microbiology (VAC)

Full metadata record

DC FieldValue Language
dc.contributor.authorDaenthanasanmak, Anusaraen
dc.contributor.authorSalguero, Gustavoen
dc.contributor.authorSundarasetty, Bala Saien
dc.contributor.authorWaskow, Claudiaen
dc.contributor.authorCosgun, Kadriye Nehiren
dc.contributor.authorGuzman, Carlos Aen
dc.contributor.authorRiese, Peggyen
dc.contributor.authorGerasch, Lauraen
dc.contributor.authorSchneider, Andreasen
dc.contributor.authorIngendoh, Alexandraen
dc.contributor.authorMesserle, Martinen
dc.contributor.authorGabaev, Ildaren
dc.contributor.authorWoelk, Bennoen
dc.contributor.authorRuggiero, Elianaen
dc.contributor.authorSchmidt, Manfreden
dc.contributor.authorvon Kalle, Christofen
dc.contributor.authorFigueiredo, Constancaen
dc.contributor.authorEiz-Vesper, Brittaen
dc.contributor.authorvon Kaisenberg, Constantinen
dc.contributor.authorGanser, Arnolden
dc.contributor.authorStripecke, Renataen
dc.date.accessioned2015-06-16T12:43:17Zen
dc.date.available2015-06-16T12:43:17Zen
dc.date.issued2015en
dc.identifier.citationEngineered dendritic cells from cord blood and adult blood accelerate effector T cell immune reconstitution against HCMV. 2015, 1:14060 Mol Ther Methods Clin Deven
dc.identifier.issn2329-0501en
dc.identifier.pmid26052526en
dc.identifier.doi10.1038/mtm.2014.60en
dc.identifier.urihttp://hdl.handle.net/10033/556994en
dc.description.abstractHuman cytomegalovirus (HCMV) harmfully impacts survival after peripheral blood hematopoietic stem cell transplantation (PB-HSCT). Delayed immune reconstitution after cord blood (CB)-HSCT leads to even higher HCMV-related morbidity and mortality. Towards a feasible dendritic cell therapy to accelerate de novo immunity against HCMV, we validated a tricistronic integrase-defective lentiviral vector (coexpressing GM-CSF, IFN-α, and HCMV pp65 antigen) capable to directly induce self-differentiation of PB and CB monocytes into dendritic cells processing pp65 ("SmyleDCpp65"). In vitro, SmyleDCpp65 resisted HCMV infection, activated CD4(+) and CD8(+) T cells and expanded functional pp65-specific memory cytotoxic T lymphocytes (CTLs). CD34(+) cells obtained from PB and CB were transplanted into irradiated NOD.Rag1(-/-).IL2γc(-/-) mice. Donor-derived SmyleDCpp65 administration after PB-HSCT stimulated peripheral immune effects: lymph node remodeling, expansion of polyclonal effector memory CD8(+) T cells in blood, spleen and bone marrow, and pp65-reactive CTL and IgG responses. SmyleDCpp65 administration after CB-HSCT significantly stimulated thymopoiesis. Expanded frequencies of CD4(+)/CD8(+) T cell precursors containing increased levels of T-cell receptor excision circles in thymus correlated with peripheral expansion of effector memory CTL responses against pp65. The comparative in vivo modeling for PB and CB-HSCT provided dynamic and spatial information regarding human T and B cell reconstitution. In vivo potency supports future clinical development of SmyleDCpp65.en
dc.language.isoenen
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/261387en
dc.rightsopenAccessen
dc.titleEngineered dendritic cells from cord blood and adult blood accelerate effector T cell immune reconstitution against HCMV.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany.en
dc.identifier.journalMolecular therapy. Methods & clinical developmenten

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