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dc.contributor.authorDaenthanasanmak, Anusara
dc.contributor.authorSalguero, Gustavo
dc.contributor.authorSundarasetty, Bala Sai
dc.contributor.authorWaskow, Claudia
dc.contributor.authorCosgun, Kadriye Nehir
dc.contributor.authorGuzman, Carlos A
dc.contributor.authorRiese, Peggy
dc.contributor.authorGerasch, Laura
dc.contributor.authorSchneider, Andreas
dc.contributor.authorIngendoh, Alexandra
dc.contributor.authorMesserle, Martin
dc.contributor.authorGabaev, Ildar
dc.contributor.authorWoelk, Benno
dc.contributor.authorRuggiero, Eliana
dc.contributor.authorSchmidt, Manfred
dc.contributor.authorvon Kalle, Christof
dc.contributor.authorFigueiredo, Constanca
dc.contributor.authorEiz-Vesper, Britta
dc.contributor.authorvon Kaisenberg, Constantin
dc.contributor.authorGanser, Arnold
dc.contributor.authorStripecke, Renata
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.
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
refterms.dateFOA2018-06-13T15:16:42Z
html.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.


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