ArticlePloS one2012
Tumor-targeted delivery of IL-2 by NKG2D leads to accumulation of antigen-specific CD8+ T cells in the tumor loci and enhanced anti-tumor effects.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
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- Interactions between vaginal local cytokine IL-2 and high-risk human papillomavirus infection with cervical intraepithelial neoplasia in a Chinese population-based study.Frontiers in cellular and infection microbiology · 2023Article
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- Cytokine Based Immunotherapy for Cancer and Lymphoma: Biology, Challenges and Future Perspectives.Frontiers in immunology · 2022Review
- Control of Tumors by Antigen-Specific CD8Journal of immunology research · 2022Article
- Natural Cyclopeptides as Anticancer Agents in the Last 20 Years.International journal of molecular sciences · 2021Review
- Chimeric Antigen Receptor Design and Efficacy in Ovarian Cancer Treatment.International journal of molecular sciences · 2021Review
- Interleukin 2-Based Fusion Proteins for the Treatment of Cancer.Journal of immunology research · 2021Review
- Sea AnemoneMolecules (Basel, Switzerland) · 2020Article
- NKG2D-Fc fusion protein promotes antitumor immunity through the depletion of immunosuppressive cells.Cancer immunology, immunotherapy : CII · 2020Article
- Immune and Inflammatory Cells in Thyroid Cancer Microenvironment.International journal of molecular sciences · 2019Review
- Fusion Proteins of NKG2D/NKG2DL in Cancer Immunotherapy.International journal of molecular sciences · 2018Review
- The toxicity study of synthesized inverse carnosine peptide analogues on HepG2 and HT-29 cells.Iranian journal of basic medical sciences · 2018Article
- Coinjection of IL2 DNA enhances E7-specific antitumor immunity elicited by intravaginal therapeutic HPV DNA vaccination with electroporation.Gene therapy · 2017Article
- Effect of targeted ovarian cancer therapy using amniotic fluid mesenchymal stem cells transfected with enhanced green fluorescent protein-human interleukin-2 in vivo.Molecular medicine reports · 2015Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Interleukin-2 (IL-2) has been shown to promote tumor-specific T-cell proliferation and differentiation but systemic administration of IL-2 results in significant toxicity. Therefore, a strategy that can specifically deliver IL-2 to the tumor location may alleviate concerns of toxicity. Because NKG2D ligands have been shown to be highly expressed in many cancer cells but not in healthy cells, we reason that a chimeric protein consisting of NKG2D linked to IL-2 will lead to the specific targeting of IL-2 to the tumor location. Therefore, we created chimeric proteins consisting of NKG2D linked to Gaussia luciferase (GLuc; a marker protein) or IL-2 to form NKG2D-Fc-GLuc and NKG2D-Fc-IL2, respectively. We demonstrated that NKG2D linked to GLuc was able to deliver GLuc to the tumor location in vivo. Furthermore, we showed that TC-1 tumor-bearing mice intramuscularly injected with DNA encoding NKG2D-Fc-IL2, followed by electroporation, exhibited an increased number of luciferase-expressing E7-specific CD8+ T cells at the tumor location. More importantly, treatment with the DNA construct encoding NKG2D-Fc-IL2 significantly enhanced the therapeutic anti-tumor effects generated by intradermal vaccination with therapeutic HPV DNA in tumor-bearing mice. Therefore, by linking NKG2D to IL2, we are able to specifically deliver IL-2 to the tumor location, enhancing antigen-specific T-cell immune response and controlling tumor growth. Our approach represents a platform technology to specifically deliver proteins of interest to tumor loci.
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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.