# Safety-switch (suicide gene) CAR-T

Source: https://onco.cc/technologies/safety-switch-car-t/  
OnCo record `safety-switch-car-t` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

A 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.

## Fields

- Kind: Technology
- Status: phase-2
- Last checked: 2026-11-03
- Also known as: suicide gene; safety switch; inducible caspase 9; iCasp9; iC9; EGFRt; truncated EGFR switch; off switch for CAR-T
- 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.
- Since: 2011
- 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

## Sources

- Di Stasi et al. 2011, NEJM: inducible apoptosis as a safety switch for adoptive cell therapy: https://doi.org/10.1056/NEJMoa1106152
- Wang et al. 2011, Blood: a transgene-encoded cell surface polypeptide (truncated EGFR) for selection, tracking and ablation of engineered cells: https://doi.org/10.1182/blood-2011-02-337360

## Connected records

- cancers: [Neuroblastoma (paediatric)](https://onco.cc/cancers/neuroblastoma/)
- fronts: [Cell Therapy](https://onco.cc/fronts/cell-therapy/)
- technologies: [Armoured, logic-gated & next-gen CARs](https://onco.cc/technologies/armored-car/), [CAR-T cell therapy](https://onco.cc/technologies/car-t/)
- drugs: [Cetuximab](https://onco.cc/drugs/cetuximab/)
- companies: [Bellicum Pharmaceuticals](https://onco.cc/companies/bellicum/)
- terms: [Cytokine release syndrome (CRS)](https://onco.cc/terms/crs/)
- trials: [GD2-CART01 (Bambino Gesù phase 1/2)](https://onco.cc/trials/gd2-cart01/)

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