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Caspase 9-Induced Apoptosis Shows Promise for Cell Therapy

Last Updated: November 02, 2011.

Incorporation of inducible caspase 9 into a transgene facilitates rapid induction of apoptosis of cells expressing the transgene with use of a dimerizing drug, according to a study published in the Nov. 3 issue of the New England Journal of Medicine.

WEDNESDAY, Nov. 2 (HealthDay News) -- Incorporation of inducible caspase 9 (iCasp9) into a transgene facilitates rapid induction of apoptosis of cells expressing the transgene with use of a dimerizing drug (AP1903), according to a study published in the Nov. 3 issue of the New England Journal of Medicine.

Antonio Di Stasi, M.D., from the Texas Children's Hospital in Houston, and colleagues investigated whether inducible caspase proteins can be used to induce apoptosis in patients receiving adoptive cell therapy. An inducible T-cell safety switch was devised by fusing human caspase 9 to a modified human FK-binding protein. The resulting transgene was introduced into donor T-cells which were given to five patients (aged 3 to 17 years) who received allogeneic stem-cell transplants for relapsed acute leukemia. Patients who developed GVHD received AP1903, and its effect on GVHD and on the function and persistence of the iCasp9 safety switch-containing cells was measured.

The investigators found that, despite their constitutive transgene expression, the iCasp9-expressing donor T cells were found in the peripheral blood of all five patients, and increased in number over time. In four patients who developed GVHD, more than 90 percent of the modified T cells were eliminated within 30 minutes of administering a single dose of AP1903, and ended the GVHD without recurrence.

"The iCasp9 cell-suicide system may increase the safety of cellular therapies and expand their clinical applications," the authors write.

Several authors disclosed financial relationships with pharmaceutical and biotechnology companies. One author disclosed involvement with a patent related to dendritic cell vaccines.

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