However, this is limited by the prolonged (>6 months) duration of lymphopenia and immunodeficiency after transplantation. One logical adjuvant approach would be to immunize the patients after HCT against a leukemia-associated antigen (LAA) such as the Wilms tumor protein 1 (WT1). Therefore, novel adjuvant approaches could be developed to enhance the GvL effect and leukemia eradication while keeping GvHD under control. Graphical abstractĭLI can improve survival, but the correlation with GvL is variable and has been associated with increased risk of GvHD. These results advocate for clinical trials testing iDCtWT1 to boost GvL and eradicate leukemia. 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. Toward clinical use, manufacturing of iDCtWT1 was up scaled and streamlined using the automated CliniMACS Prodigy system. Both humanized mouse models showed improved development and maturation of human T and B cells in the absence of adverse effects. CD34 + cell-transplanted (NRG)- and (NSG) mice expressing human leukocyte antigen (HLA)-A∗0201 (NSG-A2)-immunodeficient mice were immunized with autologous iDCtWT1. Transduction of CD14 + monocytes isolated from peripheral blood, cord blood, and leukapheresis material effectively induced their self-differentiation.

A tricistronic integrase-defective lentiviral vector produced under good manufacturing practice (GMP)-like conditions was validated. 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). 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. Acute myeloid leukemia (AML) patients with minimal residual disease and receiving allogeneic hematopoietic stem cell transplantation (HCT) have poor survival.

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