ArticleJournal of translational medicine2013
Anti-KIT designer T cells for the treatment of gastrointestinal stromal tumor.
Article in Journal of translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Current Drug Resistance Mechanisms and Treatment Options in Gastrointestinal Stromal Tumors: Summary and Update.Current treatment options in oncology · 2024Review
- The immunotherapy in gastrointestinal stromal tumors.Heliyon · 2024Review
- Molecular characteristics and immune microenvironment of gastrointestinal stromal tumours: targets for therapeutic strategies.Frontiers in oncology · 2024Review
- Advances in immunology and immunotherapy for mesenchymal gastrointestinal cancers.Molecular cancer · 2023Review
- Exploring the Dynamic Crosstalk between the Immune System and Genetics in Gastrointestinal Stromal Tumors.Cancers · 2022Review
- CSPG4 Expression in GIST Is Associated with Better Prognosis and Strong Cytotoxic Immune Response.Cancers · 2022Article
- High-Grade Endometrial Stromal Sarcoma: Molecular Alterations and Potential Immunotherapeutic Strategies.Frontiers in immunology · 2022Review
- Article
- Review
- Beyond the Driver Mutation: Immunotherapies in Gastrointestinal Stromal Tumors.Frontiers in immunology · 2021Review
- Synthetic immunology: T-cell engineering and adoptive immunotherapy.Synthetic and systems biotechnology · 2018Review
- Current status of immunotherapy for gastrointestinal stromal tumor.Cancer gene therapy · 2017Review
- Constitutive activation of oncogenic PDGFRα-mutant proteins occurring in GIST patients induces receptor mislocalisation and alters PDGFRα signalling characteristics.Cell communication and signaling : CCS · 2015Article
- Cancer immunotherapy in clinical practice -- the past, present, and future.Chinese journal of cancer · 2014Article
- MicroRNA-218 inhibits gastrointestinal stromal tumor cell and invasion by targeting KIT.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Immunotherapy for solid tumors--a review for surgeons.The Journal of surgical research · 2014Review
- Immune cells in primary and metastatic gastrointestinal stromal tumors (GIST).International journal of clinical and experimental pathology · 2014Article
- Gene-engineered T cells for cancer therapy.Nature reviews. Cancer · 2013Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImatinib mesylate is an effective treatment for metastatic gastrointestinal stromal tumor (GIST). However, most patients eventually develop resistance and there are few other treatment options. Immunotherapy using genetically modified or designer T cells (dTc) has gained increased attention for several malignancies in recent years. The aims of this study were to develop and test novel anti-KIT dTc engineered to target GIST cells.
methodsHuman anti-KIT dTc were created by retroviral transduction with novel chimeric immune receptors (CIR). The gene for stem cell factor (SCF), the natural ligand for KIT, was cloned into 1st generation (SCF-CD3ζ, 1st gen) and 2nd generation (SCF-CD28-CD3ζ, 2nd gen) CIR constructs. In vitro dTc proliferation and tumoricidal capacity in the presence of KIT+ tumor cells were measured. In vivo assessment of dTc anti-tumor efficacy was performed by treating immunodeficient mice harboring subcutaneous GIST xenografts with dTc tail vein infusions.
resultsWe successfully produced the 1st and 2nd gen anti-KIT CIR and transduced murine and human T cells. Average transduction efficiencies for human 1st and 2nd gen dTc were 50% and 42%. When co-cultured with KIT+ tumor cells, both 1st and 2nd gen dTc proliferated and produced IFNγ. Human anti-KIT dTc were efficient at lysing GIST in vitro compared to untransduced T cells. In mice with established GIST xenografts, treatment with either 1st or 2nd gen human anti-KIT dTc led to significant reductions in tumor growth rates.
conclusionsWe have constructed a novel anti-KIT CIR for production of dTc that possess specific activity against KIT+ GIST in vitro and in vivo. Further studies are warranted to evaluate the therapeutic potential and safety of anti-KIT dTc.
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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.