ReviewFrontiers in pharmacology2014
The inducible caspase-9 suicide gene system as a "safety switch" to limit on-target, off-tumor toxicities of chimeric antigen receptor T cells.
Review in Frontiers in pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 243 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
243 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Chimeric Antigen Receptor (CAR)-T Cell Immunotherapy Against Thoracic Malignancies: Challenges and Opportunities.Frontiers in immunology · 2022Pooled it
- GD2-specific chimeric antigen receptor-modified T cells for the treatment of refractory and/or recurrent neuroblastoma in pediatric patients.Journal of cancer research and clinical oncology · 2022Trial
- Ataxia-Telangiectasia, DNA Repair Deficits, Immune Dysfunction, and Cancer: A Review of Mechanisms, Clinical Presentations, and Emerging Therapies.Clinical reviews in allergy & immunology · 2026Review
- Engineering the next generation of cellular therapies for solid tumors: multi-specific armored CARs and TME reprogramming strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Cardiotoxicity of T cell immunotherapies.Nature reviews. Cardiology · 2026Review
- Applications of synthetic biology in biomedicine.Molecular biomedicine · 2026Review
- IL-15 and IL-21 synergy improves anti-tumor efficacy of iPSC-derived cytotoxic T cells in solid tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Harnessing immunity against breast cancer: from checkpoints to cell therapies.Journal of translational medicine · 2026Review
- Guided immunotherapy for residual solid tumor: integrating platelets and CAR T cells to reduce post-surgical recurrence.Biomarker research · 2026Review
- Cellular immunotherapy in melanoma: the next frontier in cancer treatment.Journal of experimental & clinical cancer research : CR · 2026Review
- Exploring CAR cell therapies beyond CAR-T for myeloid malignancies.Journal of biomedical science · 2026Review
- In Vivo mRNA-Lipid Nanoparticle CAR-T Cell Engineering: Advances, Challenges, and Clinical Translation.Biomedicines · 2026Review
- Advancing Immunotherapy in Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2026Review
- AnACS omega · 2026Article
- Are we there yet? The road to faster and more efficient CAR T cell manufacturing.Journal of biological engineering · 2026Review
- In vivo engineering of CAR-T cells: delivery strategies and clinical translation.Biomarker research · 2026Review
- FAM168B identified as a novel candidate target for chimeric antigen receptor T cell-based cancer therapy.Discover oncology · 2026Review
- CAR-engineered cell therapies: current understandings and future perspectives.Molecular biomedicine · 2026Review
- Engineering Immunity: Current Progress and Future Directions of CAR-T Cell Therapy.International journal of molecular sciences · 2026Review
- Harnessing cellular immunotherapy for cholangiocarcinoma: an integrated roadmap for overcoming resistance.Frontiers in immunology · 2026Review
183 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune modulation has become a central element in many cancer treatments, and T cells genetically engineered to express chimeric antigen receptors (CAR) may provide a new approach to cancer immunotherapy. Autologous CAR T cells that have been re-directed toward tumor-associated antigens (TAA) have shown promising results in phase 1 clinical trials, with some patients undergoing complete tumor regression. However, this T-cell therapy must carefully balance effective T-cell activation, to ensure antitumor activity, with the potential for uncontrolled activation that may produce immunopathology. An inducible Caspase 9 (iCasp9) "safety switch" offers a solution that allows for the removal of inappropriately activated CAR T cells. The induction of iCasp9 depends on the administration of the small molecule dimerizer drug AP1903 and dimerization results in rapid induction of apoptosis in transduced cells, preferentially killing activated cells expressing high levels of transgene. The iCasp9 gene has been incorporated into vectors for use in preclinical studies and demonstrates effective and reliable suicide gene activity in phase 1 clinical trials. A third-generation CAR incorporating iCasp9 re-directs T cells toward the GD2 TAA. GD2 is over-expressed in melanoma and other malignancies of neural crest origin and the safety and activity of these GD2-iCAR T cells will be investigated in CARPETS and other actively recruiting phase 1 trials.
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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.