PMID- 34095345
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221116
IS  - 2329-0501 (Print)
IS  - 2329-0501 (Electronic)
IS  - 2329-0501 (Linking)
VI  - 21
DP  - 2021 Jun 11
TI  - Induced dendritic cells co-expressing GM-CSF/IFN-alpha/tWT1 priming T and B cells and 
      automated manufacturing to boost GvL.
PG  - 621-641
LID - 10.1016/j.omtm.2021.04.004 [doi]
AB  - Acute myeloid leukemia (AML) patients with minimal residual disease and receiving 
      allogeneic hematopoietic stem cell transplantation (HCT) have poor survival. 
      Adoptive administration of dendritic cells (DCs) presenting the Wilms tumor 
      protein 1 (WT1) leukemia-associated antigen can potentially stimulate de novo T 
      and B cell development to harness the graft-versus-leukemia (GvL) effect after 
      HCT. We established a simple and fast genetic modification of monocytes for 
      simultaneous lentiviral expression of a truncated WT1 antigen (tWT1), granulocyte 
      macrophage-colony-stimulating factor (GM-CSF), and interferon (IFN)-alpha, promoting 
      their self-differentiation into potent "induced DCs" (iDCtWT1). A tricistronic 
      integrase-defective lentiviral vector produced under good manufacturing practice 
      (GMP)-like conditions was validated. Transduction of CD14(+) monocytes isolated 
      from peripheral blood, cord blood, and leukapheresis material effectively induced 
      their self-differentiation. CD34(+) cell-transplanted Nod.Rag.Gamma (NRG)- and 
      Nod.Scid.Gamma (NSG) mice expressing human leukocyte antigen (HLA)-A *0201 
      (NSG-A2)-immunodeficient mice were immunized with autologous iDCtWT1. Both 
      humanized mouse models showed improved development and maturation of human T and 
      B cells in the absence of adverse effects. Toward clinical use, manufacturing of 
      iDCtWT1 was up scaled and streamlined using the automated CliniMACS Prodigy 
      system. Proof-of-concept clinical-scale runs were feasible, and the 38-h process 
      enabled standardized production and high recovery of a cryopreserved cell product 
      with the expected identity characteristics. These results advocate for clinical 
      trials testing iDCtWT1 to boost GvL and eradicate leukemia.
CI  - (c) 2021 The Authors.
FAU - Bialek-Waldmann, Julia K
AU  - Bialek-Waldmann JK
AD  - Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, 
      Hannover Medical School, 30625 Hannover, Germany.
AD  - Laboratory of Regenerative Immune Therapies Applied, REBIRTH-Research Center for 
      Translational Regenerative Medicine, Hannover Medical School, 30625 Hannover, 
      Germany.
FAU - Domning, Sabine
AU  - Domning S
AD  - Molecular Medicine Group, School of Cancer & Pharmaceutical Sciences, Faculty of 
      Life Sciences & Medicine, Kings College London, London, UK.
FAU - Esser, Ruth
AU  - Esser R
AD  - Institute of Cellular Therapeutics, Hannover Medical School, 30625 Hannover, 
      Germany.
FAU - Glienke, Wolfgang
AU  - Glienke W
AD  - Institute of Cellular Therapeutics, Hannover Medical School, 30625 Hannover, 
      Germany.
FAU - Mertens, Mira
AU  - Mertens M
AD  - Institute of Cellular Therapeutics, Hannover Medical School, 30625 Hannover, 
      Germany.
FAU - Aleksandrova, Krasimira
AU  - Aleksandrova K
AD  - Institute of Cellular Therapeutics, Hannover Medical School, 30625 Hannover, 
      Germany.
FAU - Arseniev, Lubomir
AU  - Arseniev L
AD  - Institute of Cellular Therapeutics, Hannover Medical School, 30625 Hannover, 
      Germany.
FAU - Kumar, Suresh
AU  - Kumar S
AD  - Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, 
      Hannover Medical School, 30625 Hannover, Germany.
AD  - Laboratory of Regenerative Immune Therapies Applied, REBIRTH-Research Center for 
      Translational Regenerative Medicine, Hannover Medical School, 30625 Hannover, 
      Germany.
FAU - Schneider, Andreas
AU  - Schneider A
AD  - Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, 
      Hannover Medical School, 30625 Hannover, Germany.
AD  - Laboratory of Regenerative Immune Therapies Applied, REBIRTH-Research Center for 
      Translational Regenerative Medicine, Hannover Medical School, 30625 Hannover, 
      Germany.
FAU - Koenig, Johannes
AU  - Koenig J
AD  - Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, 
      Hannover Medical School, 30625 Hannover, Germany.
AD  - Laboratory of Regenerative Immune Therapies Applied, REBIRTH-Research Center for 
      Translational Regenerative Medicine, Hannover Medical School, 30625 Hannover, 
      Germany.
AD  - German Centre for Infection Research (DZIF), Partner site Hannover, 30625 
      Hannover, Germany.
FAU - Theobald, Sebastian J
AU  - Theobald SJ
AD  - Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, 
      Hannover Medical School, 30625 Hannover, Germany.
AD  - Laboratory of Regenerative Immune Therapies Applied, REBIRTH-Research Center for 
      Translational Regenerative Medicine, Hannover Medical School, 30625 Hannover, 
      Germany.
AD  - German Centre for Infection Research (DZIF), Partner site Hannover, 30625 
      Hannover, Germany.
FAU - Tsay, Hsin-Chieh
AU  - Tsay HC
AD  - Laboratory of Regenerative Immune Therapies Applied, REBIRTH-Research Center for 
      Translational Regenerative Medicine, Hannover Medical School, 30625 Hannover, 
      Germany.
FAU - Cornelius, Angela D A
AU  - Cornelius ADA
AD  - Laboratory of Regenerative Immune Therapies Applied, REBIRTH-Research Center for 
      Translational Regenerative Medicine, Hannover Medical School, 30625 Hannover, 
      Germany.
FAU - Bonifacius, Agnes
AU  - Bonifacius A
AD  - Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical 
      School, 30625 Hannover, Germany.
FAU - Eiz-Vesper, Britta
AU  - Eiz-Vesper B
AD  - Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical 
      School, 30625 Hannover, Germany.
FAU - Figueiredo, Constanca
AU  - Figueiredo C
AD  - Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical 
      School, 30625 Hannover, Germany.
FAU - Schaudien, Dirk
AU  - Schaudien D
AD  - Fraunhofer Institute for Toxicology and Experimental Medicine, 30625 Hannover, 
      Germany.
FAU - Talbot, Steven R
AU  - Talbot SR
AD  - Institute for Laboratory Animal Science, Hannover Medical School, 30625 Hannover, 
      Germany.
FAU - Bleich, Andre
AU  - Bleich A
AD  - Institute for Laboratory Animal Science, Hannover Medical School, 30625 Hannover, 
      Germany.
FAU - Spineli, Loukia M
AU  - Spineli LM
AD  - Department of Obstetrics, Gynecology and Reproductive Medicine, Hannover Medical 
      School, 30625 Hannover, Germany.
FAU - von Kaisenberg, Constantin
AU  - von Kaisenberg C
AD  - Department of Obstetrics, Gynecology and Reproductive Medicine, Hannover Medical 
      School, 30625 Hannover, Germany.
FAU - Clark, Caren
AU  - Clark C
AD  - Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany.
FAU - Blasczyk, Rainer
AU  - Blasczyk R
AD  - Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical 
      School, 30625 Hannover, Germany.
FAU - Heuser, Michael
AU  - Heuser M
AD  - Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, 
      Hannover Medical School, 30625 Hannover, Germany.
FAU - Ganser, Arnold
AU  - Ganser A
AD  - Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, 
      Hannover Medical School, 30625 Hannover, Germany.
FAU - Kohl, Ulrike
AU  - Kohl U
AD  - Institute of Cellular Therapeutics, Hannover Medical School, 30625 Hannover, 
      Germany.
AD  - Fraunhofer Institute for Cell Therapy and Immunology IZI and University of 
      Leipzig, 04103 Leipzig, Germany.
FAU - Farzaneh, Farzin
AU  - Farzaneh F
AD  - Molecular Medicine Group, School of Cancer & Pharmaceutical Sciences, Faculty of 
      Life Sciences & Medicine, Kings College London, London, UK.
FAU - Stripecke, Renata
AU  - Stripecke R
AD  - Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, 
      Hannover Medical School, 30625 Hannover, Germany.
AD  - Laboratory of Regenerative Immune Therapies Applied, REBIRTH-Research Center for 
      Translational Regenerative Medicine, Hannover Medical School, 30625 Hannover, 
      Germany.
AD  - German Centre for Infection Research (DZIF), Partner site Hannover, 30625 
      Hannover, Germany.
LA  - eng
GR  - BB/D014301/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - BB/E005896/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
PT  - Journal Article
DEP - 20210409
PL  - United States
TA  - Mol Ther Methods Clin Dev
JT  - Molecular therapy. Methods & clinical development
JID - 101624857
PMC - PMC8142053
OTO - NOTNLM
OT  - GMP
OT  - WT1
OT  - automated
OT  - dendritic cells
OT  - graft-versus-leukemia
OT  - immunetherapy
OT  - lentiviral vectors
OT  - leukemia
OT  - stem cell transplantation
COIS- R.S. and A.G. are co-inventors in the US- and EU-granted patent "Induced 
      Dendritic Cells and Uses Thereof," publication number WO/2014/122035; 
      PCT/EP2014/051422 (in national phases in China, Japan, and Canada). R.S. received 
      honoraria and research funding from The Jackson Laboratory, a not-for-profit 
      organization developing and commercializing humanized mouse models.
EDAT- 2021/06/08 06:00
MHDA- 2021/06/08 06:01
PMCR- 2021/04/09
CRDT- 2021/06/07 06:06
PHST- 2020/11/10 00:00 [received]
PHST- 2021/04/03 00:00 [accepted]
PHST- 2021/06/07 06:06 [entrez]
PHST- 2021/06/08 06:00 [pubmed]
PHST- 2021/06/08 06:01 [medline]
PHST- 2021/04/09 00:00 [pmc-release]
AID - S2329-0501(21)00070-X [pii]
AID - 10.1016/j.omtm.2021.04.004 [doi]
PST - epublish
SO  - Mol Ther Methods Clin Dev. 2021 Apr 9;21:621-641. doi: 
      10.1016/j.omtm.2021.04.004. eCollection 2021 Jun 11.