NCI Drug Dictionary
The NCI Drug Dictionary contains technical definitions and synonyms for drugs/agents used to treat patients with cancer or conditions related to cancer. Each drug entry includes links to check for clinical trials listed in NCI's List of Cancer Clinical Trials.
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.
Synonym: adaoviral-rheoswitch therapeutic system-human interleukin 12 Code name: INXN 2001