GM-CSF modulators(Macrophage colony stimulating factor 2 modulators), IFNA modulators(interferon alpha modulators), WT1 modulators(Wilms' Tumour 1 modulators)

Therapeutic Areas

NeoplasmsHemic and Lymphatic Diseases

Active Indication

Acute Myeloid Leukemia

Inactive Indication-

Originator Organization

King's College London

Active Organization

Hannover Medical School

King's College London

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

100 Clinical Results associated with iDCtWT1 (King's College London)

100 Translational Medicine associated with iDCtWT1 (King's College London)

100 Patents (Medical) associated with iDCtWT1 (King's College London)

Literatures (Medical) associated with iDCtWT1 (King's College London)

01 Jun 2021·Molecular Therapy - Methods & Clinical DevelopmentQ2 · MEDICINE

Induced dendritic cells co-expressing GM-CSF/IFN-α/tWT1 priming T and B cells and automated manufacturing to boost GvL

Q2 · MEDICINE

ArticleOA

Author: Köhl, Ulrike ; Koenig, Johannes ; Schneider, Andreas ; Ganser, Arnold ; Farzaneh, Farzin ; Clark, Caren ; Mertens, Mira ; Cornelius, Angela D A ; Figueiredo, Constanca ; Tsay, Hsin-Chieh ; von Kaisenberg, Constantin ; Schaudien, Dirk ; Talbot, Steven R ; Aleksandrova, Krasimira ; Heuser, Michael ; Theobald, Sebastian J ; Bleich, Andre ; Arseniev, Lubomir ; Bialek-Waldmann, Julia K ; Spineli, Loukia M ; Bonifacius, Agnes ; Domning, Sabine ; Kumar, Suresh ; Glienke, Wolfgang ; Stripecke, Renata ; Blasczyk, Rainer ; Esser, Ruth ; Eiz-Vesper, Britta

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)-α, 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.

100 Deals associated with iDCtWT1 (King's College London)

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Myeloid Leukemia	Preclinical	DE	Hannover Medical School	-
Acute Myeloid Leukemia	Preclinical	GB	King's College London	-

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iDCtWT1 (King's College London)

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Translational Medicine

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