Inducible apoptosis as a safety switch for adoptive cell therapy

Area of Science:

• Biotechnology
• Immunology
• Oncology

Background:

• Cellular therapies offer potential for cancer treatment and regenerative medicine.
• A critical need exists for rapid elimination of infused cells in case of adverse events.
• An inducible T-cell safety switch, inducible caspase 9 (iCasp9), was developed for conditional cell elimination.

Purpose of the Study:

• To test the activity and safety of the iCasp9 system in T cells for immune reconstitution.
• To evaluate the drug-induced elimination of iCasp9-expressing T cells and its effect on graft-versus-host disease (GVHD).

Main Methods:

• The iCasp9 gene was introduced into donor T cells for haploidentical stem-cell transplant recipients.
• Patients received the dimerizing drug AP1903 upon development of GVHD.
• Effects of AP1903 on GVHD, T-cell function, and persistence were measured.

Main Results:

• Five pediatric patients with relapsed acute leukemia received iCasp9-modified T cells.
• Modified T cells were detected and persisted in peripheral blood.
• A single dose of AP1903 eliminated over 90% of iCasp9 T cells within 30 minutes, resolving GVHD without recurrence.

Conclusions:

• The iCasp9 cell-suicide system enhances the safety of cellular therapies.
• This system has the potential to expand the clinical applications of cell-based treatments.
• ClinicalTrials.gov identifier: NCT00710892.