Tis10-iCasp9

**Tis10-iCasp9** (or TIS10-iCasp9) is an experimental gene therapy construct designed for targeted antineoplastic treatment, specifically in cancers that overexpress cyclooxygenase-2 (COX-2). The therapy utilizes a viral vector, typically a replication-deficient adenovirus (Ad5), to deliver a suicide gene expression cassette into target cells. This cassette features the **inducible Caspase-9 (iCasp9)** gene—a fusion of human caspase-9 and a modified human FK506-binding protein (FKBP12)—placed under the transcriptional control of the **TIS10** (also known as **COX-2** or **PTGS2**) promoter. The TIS10 promoter acts as a tumor-specific switch, restricting the expression of the iCasp9 protein to malignant cells where the promoter is highly active, while sparing healthy tissues where it is largely silent. The therapeutic effect is triggered by the administration of a small-molecule chemical inducer of dimerization (CID), such as **rimiducid (AP1903)** or **AP20187**. The CID causes the iCasp9 molecules to dimerize and activate the intrinsic apoptotic cascade, leading to the selective and rapid death of the transduced tumor cells.

Other names

TIS10-driven inducible caspase-9TIS-10-driven inducible caspase-9TIS 10-driven inducible caspase-9COX-2 promoter-driven iCasp9COX2 promoter-driven iCasp9COX 2 promoter-driven iCasp9PTGS2-iCasp9PTGS-2-iCasp9PTGS 2-iCasp9Ad-TIS10p-iCasp9Ad-TIS-10p-iCasp9Ad-TIS 10p-iCasp9