ArticleCancer immunology, immunotherapy : CII2013
Immunomodulatory activity of SGI-110, a 5-aza-2'-deoxycytidine-containing demethylating dinucleotide.
Article in Cancer immunology, immunotherapy : CII, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Incorporating DNA Methyltransferase Inhibitors (DNMTis) in the Treatment of Genitourinary Malignancies: A Systematic Review.Targeted oncology · 2018Pooled it
- A feasibility study of combined epigenetic and vaccine therapy in advanced colorectal cancer with pharmacodynamic endpoint.Clinical epigenetics · 2021Trial
- Trial
- New perspectives on DNA methylation modifications in ocular diseases.International journal of ophthalmology · 2025Review
- Immunotherapy for Treatment of Pleural Mesothelioma: Current and Emerging Therapeutic Strategies.International journal of molecular sciences · 2024Review
- The DNA methylation landscape across the TCR loci in patients with acute myeloid leukemia.International immunopharmacology · 2024Article
- Review
- DNA Methyltransferase 1 Targeting Using Guadecitabine Inhibits Prostate Cancer Growth by an Apoptosis-Independent Pathway.Cancers · 2023Article
- Guadecitabine increases response to combined anti-CTLA-4 and anti-PD-1 treatment in mouse melanoma in vivo by controlling T-cells, myeloid derived suppressor and NK cells.Journal of experimental & clinical cancer research : CR · 2023Article
- Immunotherapy of mesothelioma: the evolving change of a long-standing therapeutic dream.Frontiers in immunology · 2023Review
- Phase 1, dose-escalation study of guadecitabine (SGI-110) in combination with pembrolizumab in patients with solid tumors.Journal for immunotherapy of cancer · 2022Article
- Epigenetic Immune Remodeling of Mesothelioma Cells: A New Strategy to Improve the Efficacy of Immunotherapy.Epigenomes · 2021Article
- A stealth antigen SPESP1, which is epigenetically silenced in tumors, is a suitable target for cancer immunotherapy.Cancer science · 2021Article
- Review
- DNMT1 as a therapeutic target in pancreatic cancer: mechanisms and clinical implications.Cellular oncology (Dordrecht, Netherlands) · 2020Review
- Epigenetic reprogramming underlies efficacy of DNA demethylation therapy in osteosarcomas.Scientific reports · 2019Article
- Immunotherapy of brain metastases: breaking a "dogma".Journal of experimental & clinical cancer research : CR · 2019Review
- DNA Methyltransferase Inhibitors: Catalysts For Antitumour Immune Responses.OncoTargets and therapy · 2019Review
- Epigenetic Therapies for Acute Myeloid Leukemia and Their Immune-Related Effects.Frontiers in cell and developmental biology · 2019Review
- Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposePharmacologic DNA hypomethylation holds strong promises in cancer immunotherapy due to its immunomodulatory activity on neoplastic cells. Searching for more efficient DNA hypomethylating agents to be utilized to design novel immunotherapeutic strategies in cancer, we investigated the immunomodulatory properties of the new DNA hypomethylating agent SGI-110, that is resistant to in vivo inactivation by cytidine deaminase. EXPERIMENTAL
designCutaneous melanoma, mesothelioma, renal cell carcinoma, and sarcoma cells were treated in vitro with SGI-110. RT-PCR, quantitative RT-PCR, quantitative methylation-specific PCR, and flow cytometric analyses were performed to investigate changes induced by SGI-110 in the constitutive immune profile of cancer cells. The recognition by gp100-specific CTL of gp100-positive melanoma cells, treated or not with SGI-110, was tested by LDH release assays.
resultsSGI-110 induced/up-regulated the expression of investigated cancer/testis antigens (CTA) (i.e., MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A10, GAGE 1-2, GAGE 1-6, NY-ESO-1, and SSX 1-5) in all cancer cell lines studied, both at mRNA and at protein levels. Quantitative methylation-specific PCR analyses identified a hypomethylation of MAGE-A1 and NY-ESO-1 promoters in SGI-110-treated neoplastic cells, demonstrating a direct role of pharmacologic DNA demethylation in CTA induction. SGI-110 also up-regulated the expression of HLA class I antigens and of ICAM-1, resulting in an improved recognition of cancer cells by gp100-specific CTL.
conclusionsOur findings show that SGI-110 is a highly attractive therapeutic agent to comprehensively increase immunogenicity and immune recognition of neoplastic cells, and provide the scientific rationale for its clinical development to design novel chemo-immunotherapeutic approaches in cancer patients.
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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.