title: Engineered dendritic cells from cord blood and adult blood accelerate effector T cell immune reconstitution against HCMV.
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.
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School , Hannover, Germany.
authors.forename: Anusara
authors.initials: A
authors.lastname: Daenthanasanmak
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School , Hannover, Germany.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Salguero
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School , Hannover, Germany.
authors.forename: Bala Sai
authors.initials: BS
authors.lastname: Sundarasetty
authors.affiliation: Regeneration in Hematopoiesis, DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden , Dresden, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Waskow
authors.affiliation: Regeneration in Hematopoiesis, DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden , Dresden, Germany.
authors.forename: Kadriye Nehir
authors.initials: KN
authors.lastname: Cosgun
authors.affiliation: Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infections Research , Braunschweig, Germany.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Guzman
authors.affiliation: Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infections Research , Braunschweig, Germany.
authors.forename: Peggy
authors.initials: P
authors.lastname: Riese
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School , Hannover, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Gerasch
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School , Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneider
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School , Hannover, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Ingendoh
authors.affiliation: Institute of Virology, Hannover Medical School , Hannover, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Messerle
authors.affiliation: Institute of Virology, Hannover Medical School , Hannover, Germany.
authors.forename: Ildar
authors.initials: I
authors.lastname: Gabaev
authors.affiliation: Institute of Virology, Hannover Medical School , Hannover, Germany.
authors.forename: Benno
authors.initials: B
authors.lastname: Woelk
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center , Heidelberg, Germany.
authors.forename: Eliana
authors.initials: E
authors.lastname: Ruggiero
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center , Heidelberg, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center , Heidelberg, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: von Kalle
authors.affiliation: Department of Transfusion Medicine, Hannover Medical School , Hannover, Germany.
authors.forename: Constanca
authors.initials: C
authors.lastname: Figueiredo
authors.affiliation: Department of Transfusion Medicine, Hannover Medical School , Hannover, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Eiz-Vesper
authors.affiliation: Department of Obstetrics and Gynecology, Hannover Medical School , Hannover, Germany.
authors.forename: Constantin
authors.initials: C
authors.lastname: von Kaisenberg
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School , Hannover, Germany.
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School , Hannover, Germany.
authors.forename: Renata
authors.initials: R
authors.lastname: Stripecke