Engineered dendritic cells from cord blood and adult blood accelerate effector T cell immune reconstitution against HCMV.
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Sundarasetty, Bala Sai
Cosgun, Kadriye Nehir
Guzman, Carlos A
von Kalle, Christof
von Kaisenberg, Constantin
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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.
CitationEngineered dendritic cells from cord blood and adult blood accelerate effector T cell immune reconstitution against HCMV. 2015, 1:14060 Mol Ther Methods Clin Dev
AffiliationHelmholtz Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany.
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- Generation of lentivirus-induced dendritic cells under GMP-compliant conditions for adaptive immune reconstitution against cytomegalovirus after stem cell transplantation.
- Authors: Sundarasetty BS, Kloess S, Oberschmidt O, Naundorf S, Kuehlcke K, Daenthanasanmak A, Gerasch L, Figueiredo C, Blasczyk R, Ruggiero E, Fronza R, Schmidt M, von Kalle C, Rothe M, Ganser A, Koehl U, Stripecke R
- Issue date: 2015 Jul 22
- Integrase-defective lentiviral vectors encoding cytokines induce differentiation of human dendritic cells and stimulate multivalent immune responses in vitro and in vivo.
- Authors: Daenthanasanmak A, Salguero G, Borchers S, Figueiredo C, Jacobs R, Sundarasetty BS, Schneider A, Schambach A, Eiz-Vesper B, Blasczyk R, Weissinger EM, Ganser A, Stripecke R
- Issue date: 2012 Jul 20
- Preconditioning therapy with lentiviral vector-programmed dendritic cells accelerates the homeostatic expansion of antigen-reactive human T cells in NOD.Rag1-/-.IL-2rγc-/- mice.
- Authors: Salguero G, Sundarasetty BS, Borchers S, Wedekind D, Eiz-Vesper B, Velaga S, Jirmo AC, Behrens G, Warnecke G, Knöfel AK, Blasczyk R, Mischak-Weissinger E, Ganser A, Stripecke R
- Issue date: 2011 Oct
- Adult and Cord Blood-Derived High-Affinity gB-CAR-T Cells Effectively React Against Human Cytomegalovirus Infections.
- Authors: Olbrich H, Theobald SJ, Slabik C, Gerasch L, Schneider A, Mach M, Shum T, Mamonkin M, Stripecke R
- Issue date: 2020 Apr
- Use of a lentiviral vector encoding a HCMV-chimeric IE1-pp65 protein for epitope identification in HLA-Transgenic mice and for ex vivo stimulation and expansion of CD8(+) cytotoxic T cells from human peripheral blood cells.
- Authors: Rohrlich PS, Cardinaud S, Lulè J, Montero-Julian FA, Prodhomme V, Firat H, Davignon JL, Perret E, Monseaux S, Necker A, Michelson S, Lemonnier FA, Charneau P, Davrinche C
- Issue date: 2004 May