Preferred Label : Ad-RTS-hIL-12;
NCIt synonyms : Adenoviral- RheoSwitch Therapeutic System-Human Interleukin 12;
NCIt definition : An inducible adenoviral vector encoding human pro-inflammatory cytokine interleukin-12
(IL-12; IL12), which is under the transcriptional control of the RheoSwitch Therapeutic
System (RTS) (Ad-RTS-hIL-12), with potential immunomodulating and antineoplastic activities.
RTS consists of two fusion proteins: Gal4-EcR, which contains a modified ecdysone
receptor (EcR) fused with the DNA binding domain of the yeast Gal4 transcription factor,
and VP16-RXR, which contains a chimeric retinoid X receptor (RXR) fused with the transcription
activation domain of the viral protein VP16 of herpes simplex virus type 1 (HSV1).
Upon intratumoral administration of Ad-RTS-hIL-12, given in combination with the proprietary,
diacylhydrazine-based activator ligand veledimex (INXN-1001), veledimex binds specifically
to the EcR part of the RTS and stabilizes heterodimerization between the two fusion
proteins, forming an active transcription factor, which induces the transcription
of IL-12 under the control of an inducible promoter containing Gal4-binding sites.
The expressed IL-12 activates the immune system by promoting the activation of natural
killer cells (NK cells), inducing secretion of interferon-gamma (IFN-g) and inducing
cytotoxic T-lymphocyte (CTL)-mediated responses against tumor cells, which may result
in immune-mediated tumor cell lysis and inhibition of tumor cell proliferation. In
the presence of veledimex, the protein heterodimer changes to a stable conformation
and can bind to the inducible promoter, while without veledimex the two fusion proteins
form unstable heterodimers; this allows the controlled, regulated intratumoral expression
of the IL-12 gene.;
Molecule name : INXN-2001; INXN 2001;
NCI Metathesaurus CUI : CL542155;
Origin ID : C143953;
UMLS CUI : C4685001;
Semantic type(s)
- concept_is_in_subset
- has_target
