ArticleGene therapy2001
Gene transfer of antisense hypoxia inducible factor-1 alpha enhances the therapeutic efficacy of cancer immunotherapy.
Article in Gene therapy, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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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.
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Who cites it
44 citing papers in PubMed, 142 citations in OpenAlex.
- Hypoxic tumor microenvironment and immune cell dynamics: From metabolic reprogramming to therapeutic innovation.Iranian journal of basic medical sciences · 2026Review
- Targeting hypoxia-inducible factor 1 alpha augments synergistic effects of chemo/immunotherapy via modulating tumor microenvironment in a breast cancer mouse model.BioImpacts : BI · 2025Article
- Associations between HIFs and tumor immune checkpoints: mechanism and therapy.Discover oncology · 2024Review
- Hypoxia within the glioblastoma tumor microenvironment: a master saboteur of novel treatments.Frontiers in immunology · 2024Review
- HIF 1 α - a promising target for the treatment of meningiomas.Medicine and pharmacy reports · 2023Article
- Addressing Natural Killer Cell Dysfunction and Plasticity in Cell-Based Cancer Therapeutics.Cancers · 2023Review
- Reprogramming the tumor microenvironment to improve the efficacy of cancer immunotherapies.Medical oncology (Northwood, London, England) · 2022Review
- Action Sites and Clinical Application of HIF-1α Inhibitors.Molecules (Basel, Switzerland) · 2022Review
- Identification and validation of a hypoxia-immune signature for overall survival prediction in lung adenocarcinoma.Frontiers in genetics · 2022Article
- Targeting hypoxia in the tumor microenvironment: a potential strategy to improve cancer immunotherapy.Journal of experimental & clinical cancer research : CR · 2021Review
- Role of hypoxia inducible factor-1 in cancer stem cells (Review).Molecular medicine reports · 2021Review
- Cell-Based Nanoparticles Delivery Systems for Targeted Cancer Therapy: Lessons from Anti-Angiogenesis Treatments.Molecules (Basel, Switzerland) · 2020Review
- Up-regulation of hypoxia-inducible factor antisense as a novel approach to treat ovarian cancer.Theranostics · 2020Article
- The influence of microenvironment on tumor immunotherapy.The FEBS journal · 2019Review
- HIF-1α-derived cell-penetrating peptides inhibit ERK-dependent activation of HIF-1 and trigger apoptosis of cancer cells under hypoxia.Cellular and molecular life sciences : CMLS · 2019Article
- Microvascular bioengineering: a focus on pericytes.Journal of biological engineering · 2019Review
- Hypoxia inducible factors in hepatocellular carcinoma.Oncotarget · 2017Review
- Development of Inhibitors Targeting Hypoxia-Inducible Factor 1 and 2 for Cancer Therapy.Yonsei medical journal · 2017Review
- Reprogramming the Transcriptional Response to Hypoxia with a Chromosomally Encoded Cyclic Peptide HIF-1 Inhibitor.ACS synthetic biology · 2017Article
- Critical Role of Tumor Microenvironment in Shaping NK Cell Functions: Implication of Hypoxic Stress.Frontiers in immunology · 2015Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Solid tumors meet their demands for nascent blood vessels and increased glycolysis, to combat hypoxia, by activating multiple genes involved in angiogenesis and glucose metabolism. Hypoxia inducible factor-1 (HIF-1) is a constitutively expressed basic helix-loop-helix transcription factor, formed by the assembly of HIF-1alpha and HIF-1beta (Arnt), that is stablized in response to hypoxia, and rapidly degraded under normoxic conditions. It activates the transcription of genes important for maintaining oxygen homeostasis. Here, we demonstrate that engineered down-regulation of HIF-1alpha by intratumoral gene transfer of an antisense HIF-1alpha plasmid leads to the down-regulation of VEGF, and decreased tumor microvessel density. Antisense HIF-1alpha monotherapy resulted in the complete and permanent rejection of small (0.1 cm in diameter) EL-4 tumors, which is unusual for an anti-angiogenic agent where transient suppression of tumor growth is the norm. It induced NK cell-dependent rejection of tumors, but failed to stimulate systemic T cell-mediated anti-tumor immunity, and synergized with B7-1-mediated immunotherapy to cause the NK cell and CD8 T cell-dependent rejection of larger EL-4 tumors (0.4 cm in diameter) that were refractory to monotherapies. Mice cured of their tumors by combination therapy resisted a rechallenge with parental tumor cells, indicating systemic antitumor immunity had been achieved. In summary, whilst intensive investigations are in progress to target the many HIF-1 effectors, the results herein indicate that blocking hypoxia-inducible pathways and enhancing NK-mediated antitumor immunity by targeting HIF-1 itself may be advantageous, especially when combined with cancer immunotherapy.
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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.