ArticleHuman gene therapy2013
Chimeric NKG2D CAR-expressing T cell-mediated attack of human ovarian cancer is enhanced by histone deacetylase inhibition.
Article in Human gene therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 107 citations in OpenAlex.
- Harnessing the NKG2D immune surveillance pathway using engineered T-cells for the treatment of human disease.Human vaccines & immunotherapeutics · 2026Review
- Epigenetic modulation of NKG2D ligands enhances NKG2D-CAR T cell efficacy in neuroblastoma.Journal of translational medicine · 2026Article
- Targeting NKG2DLs with an ADCC enhanced fusion protein for induction of NK cell reactivity against ovarian cancer.Journal of ovarian research · 2026Article
- Targeting NKG2D/NKG2DL axis in cancer immunotherapy: mechanisms and therapeutic applications.Journal of translational medicine · 2026Review
- NKG2D CAR-T cells for solid tumor immunotherapy: advances, challenges, and future directions.Frontiers in immunology · 2026Review
- The Metabolic Regulation of the NKG2D-Positive NK and T Cells and Their Role in Disease Progression.Biomolecules · 2025Review
- A Novel Early Memory-Enriched Allogeneic NKG2D CAR-T Cell Therapy Based on CRISPR/Cas9 Technology for Solid Tumors.Cancers · 2025Article
- Epigenetic regulation in gynecological cancers: a paradigm shift in immunotherapy strategies.Journal of experimental & clinical cancer research : CR · 2025Review
- Designs of NKG2D-based immunotherapeutics for cancer.Frontiers in immunology · 2025Review
- Harnessing NKG2D CAR-T cells with radiotherapy: a novel approach for esophageal squamous cell carcinoma treatment.Frontiers in immunology · 2025Article
- Solid tumor immunotherapy using NKG2D-based adaptor CAR T cells.Cell reports. Medicine · 2024Article
- Efficacy of NKG2D CAR-T cells with IL-15/IL-15Rα signaling for treating Epstein-Barr virus-associated lymphoproliferative disorder.Experimental hematology & oncology · 2024Article
- Chimeric antigen receptor-induced antigen loss protects CD5.CART cells from fratricide without compromising on-target cytotoxicity.Cell reports. Medicine · 2024Article
- Natural killer cells in cancer immunotherapy.MedComm · 2024Review
- shRNA-mediated gene silencing of HDAC11 empowers CAR-T cells against prostate cancer.Frontiers in immunology · 2024Article
- Sodium valproate enhances efficacy of NKG2D CAR-T cells against glioblastoma.Frontiers in immunology · 2024Article
- Chimeric antigen receptor-natural killer cells: a promising sword against insidious tumor cells.Human cell · 2023Review
- Reliable Hallmarks and Biomarkers of Senescent Lymphocytes.International journal of molecular sciences · 2023Review
- Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia.Journal for immunotherapy of cancer · 2023Article
- CX3CR1 deficiency-induced TIL tumor restriction as a novel addition for CAR-T design in solid malignancies.iScience · 2023Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
NKG2D ligands (NKG2DLs) are widely expressed on ovarian cancers to various degrees, making them attractive targets for immunotherapy. Here, we applied a chimeric antigen receptor (CAR) approach for the targeting of NKG2DLs expressed on human ovarian cancer cells and evaluated the impact of pharmacological upregulation of NKG2DLs on immune recognition. Various NKG2DLs, including MICA/B and ULBP-1, -2, -3, and -4, were expressed at various levels on the surface of all established ovarian cancer cell lines and primary ovarian cancer samples tested. To redirect human T cells against NKG2DLs, an NKG2DL-specific CAR was generated by fusing the extracellular domain of the NKG2D receptor to the 4-1BB costimulatory and CD3-ζ chain signaling domains. In vitro expansion of chimeric NKG2D CAR T cells was delayed compared with untransduced T cells and control CAR T cells; the likely result of fratricide among activated T cells expressing NKG2DLs. However, NKG2D CAR T cells did expand and were selectively enriched during prolonged culture. In coculture, CD4(+) and CD8(+) NKG2D CAR T cells specifically recognized and killed NKG2DL-expressing ovarian cancer cell lines but not NKG2DL-negative cells. Notably, pretreatment of ovarian cancer cells expressing moderate to low levels of NKG2DLs with the histone deacetylase inhibitor sodium valproate (VPA) upregulated NKG2DL cell surface expression and consequently enhanced their immune recognition by chimeric NKG2D CAR T cells. Our results demonstrate that VPA-induced upregulation of NKG2DL expression enhances the immune recognition of ovarian cancer cells by engineered NKG2D CAR T cells, and rationalizes the use of VPA in combination with NKG2DL-targeted immunotherapy in ovarian cancer.
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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.