Journal article

Phase I Trial of Inducible Caspase 9 T Cells in Adult Stem Cell Transplant Demonstrates Massive Clonotypic Proliferative Potential and Long-term Persistence of Transgenic T Cells

Ping Zhang, Jyothy Raju, Md Ashik Ullah, Raymond Au, Antiopi Varelias, Kate H Gartlan, Stuart D Olver, Luke D Samson, Elise Sturgeon, Nienke Zomerdijk, Judy Avery, Tessa Gargett, Michael P Brown, Lachlan J Coin, Devika Ganesamoorthy, Cheryl Hutchins, Gary R Pratt, Glen A Kennedy, A James Morton, Cameron I Curley Show all



PURPOSE: Inducible caspase 9 (iCasp9) is a cellular safety switch that can make T-cell therapy safer. The purpose of this phase I trial was to investigate the use of iCasp9-transduced T-cell addback in adult patients undergoing haploidentical stem cell transplantation for high-risk hematologic malignancies. PATIENTS AND METHODS: Patients undergoing myeloablative, CD34-selected haploidentical stem cell transplantation were treated with 0.5-1.0 × 106/kg donor-derived iCasp9-transduced T cells on day +25 or 26 post-transplant, with additional doses allowed for disease relapse, infection, or mixed chimerism. RESULTS: Three patients were enrolled. iCasp9-transduced T cells were readily detectable..

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Awarded by National Health and Medical Research Council (NHMRC, Australia)

Awarded by NH&MRC Early Career Fellowship

Funding Acknowledgements

The authors are thankful to the patients and their families for their participation and cooperation. The authors thank Prof. Malcolm K Brenner at the Center for Cell and Gene Therapy (Baylor College of Medicine, Houston, TX) for the manufacture of clinical grade retrovirus vector. The authors thank Bellicum Pharmaceuticals for providing AP1903 (Rimiducid). This study was supported by a Project Grant (APP1053135) from the National Health and Medical Research Council (NH&MRC, Australia), QIMR Berghofer Ride To Conquer Cancer Flagship Award and Royal Brisbane, and Women's Hospital Foundation. S.-K. Tey was supported by an NH&MRC Early Career Fellowship (APP1054786) and G.R. Hill was supported by a Queensland Health Senior Clinical Research Fellowship.