Engineered dendritic cells from cord blood and adult blood accelerate effector T cell immune reconstitution against HCMV.
dc.contributor.author | Daenthanasanmak, Anusara | |
dc.contributor.author | Salguero, Gustavo | |
dc.contributor.author | Sundarasetty, Bala Sai | |
dc.contributor.author | Waskow, Claudia | |
dc.contributor.author | Cosgun, Kadriye Nehir | |
dc.contributor.author | Guzman, Carlos A | |
dc.contributor.author | Riese, Peggy | |
dc.contributor.author | Gerasch, Laura | |
dc.contributor.author | Schneider, Andreas | |
dc.contributor.author | Ingendoh, Alexandra | |
dc.contributor.author | Messerle, Martin | |
dc.contributor.author | Gabaev, Ildar | |
dc.contributor.author | Woelk, Benno | |
dc.contributor.author | Ruggiero, Eliana | |
dc.contributor.author | Schmidt, Manfred | |
dc.contributor.author | von Kalle, Christof | |
dc.contributor.author | Figueiredo, Constanca | |
dc.contributor.author | Eiz-Vesper, Britta | |
dc.contributor.author | von Kaisenberg, Constantin | |
dc.contributor.author | Ganser, Arnold | |
dc.contributor.author | Stripecke, Renata | |
dc.date.accessioned | 2015-06-16T12:43:17Z | en |
dc.date.available | 2015-06-16T12:43:17Z | en |
dc.date.issued | 2015 | en |
dc.identifier.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 | en |
dc.identifier.issn | 2329-0501 | en |
dc.identifier.pmid | 26052526 | en |
dc.identifier.doi | 10.1038/mtm.2014.60 | en |
dc.identifier.uri | http://hdl.handle.net/10033/556994 | en |
dc.description.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. | |
dc.language.iso | en | en |
dc.relation | info:eu-repo/grantAgreement/EC/FP7/261387 | en |
dc.rights | openAccess | en |
dc.title | Engineered dendritic cells from cord blood and adult blood accelerate effector T cell immune reconstitution against HCMV. | en |
dc.type | Article | en |
dc.contributor.department | Helmholtz Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany. | en |
dc.identifier.journal | Molecular therapy. Methods & clinical development | en |
refterms.dateFOA | 2018-06-13T15:16:42Z | |
html.description.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. |