Preferred Label : Autologous CD34 -enriched HSPCs Transduced with VSV-G Encoding IFN-a2;
NCIt definition : A preparation of autologous CD34 -enriched hematopoietic stem and progenitor cells
(HSPCs) that are genetically modified with a vesicular stomatitis virus-G (VSV-G)
pseudo-typed lentiviral vector encoding for the human cytokine interferon-alpha 2
(IFN-a2) gene, with potential immunostimulating and antineoplastic activities. The
expression of IFN-a2 is tightly controlled by the human angiopoietin receptor Tie2
enhancer/promoter sequence, found in the tumor-infiltrating macrophages Tie2 expressing
monocytes (TEMs), and is under microRNA-126 (miR-126)-mediated control. This enables
suppression of IFN-a2 expression in HSPCs while IFN-a2 is selectively expressed in
TEMs. Upon administration of the autologous CD34 -enriched HSPCs transduced with VSV-G
encoding IFN-a2, the HSPCs travel to the bone marrow and differentiate into various
cells including monocytes and macrophages. These cells travel to the tumor microenvironment
(TME), and the TEMs, capable of expressing IFN-a2, specifically release IFN-a2 in
the TME. IFN-2a binds to specific IFN cell-surface receptors, and activates IFN-mediated
signal transduction, resulting in the transcription and translation of genes containing
an interferon-specific response element whose protein products mediate anticancer
and anti-angiogenic effects. This results in the induction of both G2 cell cycle arrest
and apoptosis in tumor cells. In addition, IFN-a2 triggers an indirect anti-tumor
immune response involving the activation of natural killer (NK) cells and dendritic
cells (DCs), and the induction of immune effector cell cytotoxicity, thereby further
killing tumor cells. TEMs, a subset of tumor-infiltrating macrophages characterized
by expression of the tyrosine protein kinase angiopoietin receptor Tie2, are upregulated
in the TME while infrequently found in normal organs. TEMs promote tumor angiogenesis.;
Drug name : Temferon;
NCI Metathesaurus CUI : CL1406218;
Origin ID : C172105;
UMLS CUI : C5419454;
Semantic type(s)
- Cell [UMLS semantic type]
- concept_is_in_subset
