ArticleCancer gene therapy2014
Bortezomib sensitizes non-small cell lung cancer to mesenchymal stromal cell-delivered inducible caspase-9-mediated cytotoxicity.
Article in Cancer gene therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Mesenchymal stem cells in preclinical cancer cytotherapy: a systematic review.Stem cell research & therapy · 2018Pooled it
- Dual-antigen recognition iPSC-derived CAR-T cells for B-cell malignancies: establishment of a COVID-19 vaccine synergy strategy.Frontiers in cell and developmental biology · 2026Article
- The concealed side of caspases: beyond a killer of cells.Cellular and molecular life sciences : CMLS · 2024Review
- Engineered Mesenchymal Stem Cells as Treatment for Cancers: Opportunities, Clinical Applications and Challenges.The Malaysian journal of medical sciences : MJMS · 2024Review
- iPSC-derived hypoimmunogenic tissue resident memory T cells mediate robust anti-tumor activity against cervical cancer.Cell reports. Medicine · 2023Article
- The Dual Role of Mesenchymal Stem Cells in Cancer Pathophysiology: Pro-Tumorigenic Effects versus Therapeutic Potential.International journal of molecular sciences · 2023Review
- Dual-antigen targeted iPSC-derived chimeric antigen receptor-T cell therapy for refractory lymphoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Review
- Combinatorial suicide gene strategies for the safety of cell therapies.Frontiers in immunology · 2022Article
- Exogenous Introduction of Initiator and Executioner Caspases Results in Different Apoptotic Outcomes.JACS Au · 2021Article
- Mesenchymal stromal cell delivery of oncolytic immunotherapy improves CAR-T cell antitumor activity.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Sustainable Tumor-Suppressive Effect of iPSC-Derived Rejuvenated T Cells Targeting Cervical Cancers.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Inhibition of USP14 induces ER stress-mediated autophagy without apoptosis in lung cancer cell line A549.Cell stress & chaperones · 2020Article
- Targeting apoptotic caspases in cancer.Biochimica et biophysica acta. Molecular cell research · 2020Review
- The structure and regulation of the E3 ubiquitin ligase HUWE1 and its biological functions in cancer.Investigational new drugs · 2020Review
- Rapid Regulation of Human Mesenchymal Stem Cell Proliferation Using Inducible Caspase-9 Suicide Gene for Safe Cell-Based Therapy.International journal of molecular sciences · 2019Article
- Synergistic Effects of Bortezomib-OV Therapy and Anti-Invasive Strategies in Glioblastoma: A Mathematical Model.Cancers · 2019Article
- Sclareol inhibits cell proliferation and sensitizes cells to the antiproliferative effect of bortezomib via upregulating the tumor suppressor caveolin-1 in cervical cancer cells.Molecular medicine reports · 2017Article
- Fail-Safe System against Potential Tumorigenicity after Transplantation of iPSC Derivatives.Stem cell reports · 2017Article
- Engineered Mesenchymal Stem Cells as an Anti-Cancer Trojan Horse.Stem cells and development · 2016Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Delivery of suicide genes to solid tumors represents a promising tumor therapy strategy. However, slow or limited killing by suicide genes and ineffective targeting of the tumor has reduced effectiveness. We have adapted a suicide system based on an inducible caspase-9 (iC9) protein that is activated using a specific chemical inducer of dimerization (CID) for adenoviral-based delivery to lung tumors via mesenchymal stromal cells (MSCs). Four independent human non-small cell lung cancer (NSCLC) cell lines were transduced with adenovirus encoding iC9, and all underwent apoptosis when iC9 was activated by adding CID. However, there was a large variation in the percentage of cell killing induced by CID across the different lines. The least responsive cell lines were sensitized to apoptosis by combined inhibition of the proteasome using bortezomib. These results were extended to an in vivo model using human NSCLC xenografts. E1A-expressing MSCs replicated Ad.iC9 and delivered the virus to lung tumors in SCID mice. Treatment with CID resulted in some reduction of tumor growth, but addition of bortezomib led to greater reduction of tumor size. The enhanced apoptosis and anti-tumor effect of combining MSC-delivered Ad.iC9, CID and bortezomib appears to be due to increased stabilization of active caspase-3, as proteasomal inhibition increased the levels of cleaved caspase-9 and caspase-3. Knockdown of X-linked inhibitor of apoptosis protein (XIAP), a caspase inhibitor that targets active caspase-3 to the proteasome, also sensitized iC9-transduced cells to CID, suggesting that blocking the proteasome counteracts XIAP to permit apoptosis. Thus, MSC-based delivery of the iC9 suicide gene to human NSCLC effectively targets lung cancer cells for elimination. Combining this therapy with bortezomib, a drug that is otherwise inactive in this disease, further enhances the anti-tumor activity of this strategy.
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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.