{"entity":{"id":"safety-switch-car-t","kind":"technology","name":"Safety-switch (suicide gene) CAR-T","aka":["suicide gene","safety switch","inducible caspase 9","iCasp9","iC9","EGFRt","truncated EGFR switch","off switch for CAR-T"],"tldr":"An extra gene built into engineered immune cells that lets doctors destroy those cells quickly with a drug if they start causing serious harm. It is an off switch for a living medicine.","summary":"Engineered T cells keep dividing after infusion, so a severe toxicity cannot be stopped by withholding the next dose. Safety switches add a way to remove the cells. The inducible caspase 9 (iCasp9) switch fuses human caspase 9 to a modified FK-binding protein; a bioinert dimerising drug (AP1903, later named rimiducid) activates it. In the first clinical test (Di Stasi and colleagues, Baylor College of Medicine, NEJM 2011), donor T cells carrying the switch were given to five children and young people after haploidentical stem cell transplant for relapsed acute leukaemia; in the four who developed graft-versus-host disease, a single dose of the drug eliminated more than 90 per cent of the modified T cells within 30 minutes and ended the disease without recurrence.\n\nA second approach co-expresses a truncated EGFR (EGFRt) that has lost its signalling domain but keeps the epitope for cetuximab, so the same marker serves for selecting, tracking and, through antibody-dependent cytotoxicity, eliminating the cells (Wang and colleagues, Blood 2011). iCasp9 has been built into CAR-T products, including the GD2-CART01 cells used for relapsed neuroblastoma at Bambino Gesù, where the switch was available but not needed.","status":"phase-2","asOf":"2026-11-03","links":[{"label":"Di Stasi et al. 2011, NEJM: inducible apoptosis as a safety switch for adoptive cell therapy","url":"https://doi.org/10.1056/NEJMoa1106152"},{"label":"Wang et al. 2011, Blood: a transgene-encoded cell surface polypeptide (truncated EGFR) for selection, tracking and ablation of engineered cells","url":"https://doi.org/10.1182/blood-2011-02-337360"}],"tags":[],"related":[],"cancers":["neuroblastoma"],"sections":["cell-therapy"],"technologies":["car-t","armored-car"],"targets":[],"drugs":["cetuximab"],"companies":["bellicum"],"institutions":[],"pathways":[],"terms":["crs"],"trials":["gd2-cart01"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A transgene co-expressed with the CAR makes the cells killable on demand: a chemically induced dimeriser activates a caspase (iCasp9), or an approved antibody binds a surface tag (truncated EGFR, CD20 mimotopes) and recruits immune killing.","strengths":["Rapid elimination of cells in a toxicity crisis","Uses inert or already approved drugs","Can make bolder CAR designs acceptable to regulators"],"limitations":["Activating the switch ends the therapy as well as the toxicity","Elimination may be incomplete","Adds size to the genetic cargo"],"since":2011},"route":"/technologies/safety-switch-car-t/","neighbours":{"cancer":[{"id":"neuroblastoma","kind":"cancer","name":"Neuroblastoma (paediatric)","route":"/cancers/neuroblastoma/"}],"section":[{"id":"cell-therapy","kind":"section","name":"Cell Therapy","route":"/fronts/cell-therapy/"}],"technology":[{"id":"armored-car","kind":"technology","name":"Armoured, logic-gated & next-gen CARs","route":"/technologies/armored-car/"},{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"}],"drug":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"}],"company":[{"id":"bellicum","kind":"company","name":"Bellicum Pharmaceuticals","route":"/companies/bellicum/"}],"term":[{"id":"crs","kind":"term","name":"Cytokine release syndrome (CRS)","route":"/terms/crs/"}],"trial":[{"id":"gd2-cart01","kind":"trial","name":"GD2-CART01 (Bambino Gesù phase 1/2)","route":"/trials/gd2-cart01/"}]}}