Improving the safety of T-Cell therapies using an inducible caspase-9 gene.
Improving the safety of T-Cell therapies using an inducible caspase-9 gene.
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DOI：
10.1016/j.exphem.2016.07.011
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发表时间：
2016-11
影响因子：
2.6
通讯作者：
Brenner, Malcolm K.
中科院分区：
文献类型：
--
作者：
Zhou, Xiaoou;Brenner, Malcolm K.
Adoptive transfer of T cells can be an effective anti-cancer treatment. However, uncontrolled or unpredictable immediate or persistent toxicities are a source of concern. The ability to conditionally eliminate aberrant cells in vivo therefore is becoming a critical step for the successful translation of this approach to the clinic. We review the evolution of safety systems, focusing on a suicide switch that can be expressed stably and efficiently in human T cells without impairing phenotype, function or antigen specificity. This system is based on the fusion of human caspase 9 to a modified human FK-binding protein, allowing conditional dimerization in the presence of an otherwise bioinert small molecule drug. When exposed to the synthetic dimerizing drug, the inducible caspase 9 (iC9) becomes activated and leads to the rapid apoptosis of cells expressing this construct. We have demonstrated the clinical feasibility and efficacy of this approach after haploidentical hematopoietic stem cell transplant (haplo-HSCT). Here we review the benefits and limitations of the approach.
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通讯作者：
Cavazzana-Calvo, M
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Sadelain M
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Sadelain M
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45.3
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Gottschalk, Stephen