ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
Serial Activation of the Inducible Caspase 9 Safety Switch After Human Stem Cell Transplantation.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 37 citations in OpenAlex.
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- Skeletal muscle reprogramming in peripheral nerve injury: mechanisms, therapeutic roles, and complication management.Experimental biology and medicine (Maywood, N.J.) · 2026Review
- Truncated form of human CD19 antigen as a suicide gene to control T-cell alloreactivity: ΔHaematologica · 2025Article
- Caspase 9-induced apoptosis enables efficient fetal cell ablation and disease modeling.Nature communications · 2025Article
- Sequential Stem Cell-Kidney Transplantation in Schimke Immuno-osseous Dysplasia.The New England journal of medicine · 2022Article
- Inducible caspase-9 suicide gene under control of endogenous oct4 to safeguard mouse and human pluripotent stem cell therapy.Molecular therapy. Methods & clinical development · 2022Article
- Tumorigenicity risk of iPSCsPrecision clinical medicine · 2022Review
- Combinatorial suicide gene strategies for the safety of cell therapies.Frontiers in immunology · 2022Article
- Review
- Current Limitations and Perspectives of Chimeric Antigen Receptor-T-Cells in Acute Myeloid Leukemia.Cancers · 2021Review
- Review
- Inclusion of the Inducible Caspase 9 Suicide Gene in CAR Construct Increases Safety of CAR.CD19 T Cell Therapy in B-Cell Malignancies.Frontiers in immunology · 2021Article
- Depletion of T cellsFrontiers in immunology · 2021Article
- Precision installation of a highly efficient suicide gene safety switch in human induced pluripotent stem cells.Stem cells translational medicine · 2020Article
- Identification of dual positive CD19+/CD3+ T cells in a leukapheresis product undergoing CAR transduction: a case report.Journal for immunotherapy of cancer · 2020Article
- Genetically Modified T-Cell Therapy for Osteosarcoma: Into the Roaring 2020s.Advances in experimental medicine and biology · 2020Review
- Regulated ex vivo regional gene therapy for bone repair using an inducible caspase-9 suicide gene system.Gene therapy · 2019Article
- Engineering for Success: Approaches to Improve Chimeric Antigen Receptor T Cell Therapy for Solid Tumors.Drugs · 2019Review
- Chimeric antigen receptor T-cell approaches to HIV cure.Current opinion in HIV and AIDS · 2018Review
- A Versatile Safeguard for Chimeric Antigen Receptor T-Cell Immunotherapies.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Activation of the inducible caspase 9 (iC9) safety gene by a dimerizing drug (chemical inducer of dimerization (CID) AP1903) effectively resolves the symptoms and signs of graft-versus-host disease (GvHD) in haploidentical stem cell transplant (HSCT) recipients. However, after CID treatment, 1% of iC9-T cells remain and can regrow over time; although these resurgent T cells do not cause recurrent GvHD, it remains unclear whether repeat CID treatments are a safe and feasible way to further deplete residual gene-modified T cells should any other adverse effects associated with them occur. Here, we report a patient who received an infusion of haploidentical iC9-T cells after HSCT and subsequently received three treatments with AP1903. There was a mild (grade 2) and transient pancytopenia following each AP1903 administration but no non-hematological toxicity. Ninety five percent of circulating iC9-T cells (CD3(+)CD19(+)) were eliminated after the first AP1903 treatment. Three months later, the residual cells had expanded more than eightfold and had a lower level of iC9 expression. Each repeated AP1903 administration eliminated a diminishing percentage of the residual repopulating cells, but elimination could be enhanced by T-cell activation. These data support the safety and efficiency of repeated CID treatments for persistent or recurring toxicity from T-cell therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.