ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
T Cells Engineered With Chimeric Antigen Receptors Targeting NKG2D Ligands Display Lethal Toxicity in Mice.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 75 citations in OpenAlex.
- Harnessing the NKG2D immune surveillance pathway using engineered T-cells for the treatment of human disease.Human vaccines & immunotherapeutics · 2026Review
- CAR-T cell therapy for pediatric solid tumors: armored CAR-T cells and beyond.Cancer metastasis reviews · 2026Review
- Novel Combination of Irreversible Electroporation and Allogenic Chimeric Antigen Receptor T-Cell Therapy Synergizes Therapeutic Outcomes in a Preclinical Human Pancreatic Cancer Mouse Model.Research (Washington, D.C.) · 2026Article
- Targeting pyruvate metabolism generates distinct CD8+ T cell responses to gammaherpesvirus and B lymphoma.JCI insight · 2025Article
- 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
- The efficacy and applicability of chimeric antigen receptor (CAR) T cell-based regimens for primary bone tumors: A comprehensive review of current evidence.Journal of bone oncology · 2024Review
- Targeting senescent cells with NKG2D-CAR T cells.Cell death discovery · 2024Article
- Engineered T cells for Colorectal Cancer.Immunotherapy · 2024Review
- A novel strategy of co-expressing CXCR5 and IL-7 enhances CAR-T cell effectiveness in osteosarcoma.Frontiers in immunology · 2024Article
- Article
- The Regenerative Power of Stem Cells: Treating Bleomycin-Induced Lung Fibrosis.Stem cells and cloning : advances and applications · 2023Review
- Current status and future challenges of CAR-T cell therapy for osteosarcoma.Frontiers in immunology · 2023Review
- Dual CAR-T cells to treat cancers co-expressing NKG2D and PD1 ligands in xenograft models of peritoneal metastasis.Cancer immunology, immunotherapy : CII · 2023Article
- Time 2EVOLVE: predicting efficacy of engineered T-cells - how far is the bench from the bedside?Journal for immunotherapy of cancer · 2022Review
- Time to evolve: predicting engineered T cell-associated toxicity with next-generation models.Journal for immunotherapy of cancer · 2022Review
- Review
- Chimeric non-antigen receptors in T cell-based cancer therapy.Journal for immunotherapy of cancer · 2021Review
- Cancer stem cell-targeted chimeric antigen receptor (CAR)-T cell therapy: Challenges and prospects.Acta pharmaceutica Sinica. B · 2021Review
- Engineering of chimeric natural killer cell receptors to develop precision adoptive immunotherapies for cancer.Clinical and experimental immunology · 2020Review
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Ligands for the NKG2D receptor are overexpressed on tumors, making them interesting immunotherapy targets. To assess the tumoricidal properties of T cells directed to attack NKG2D ligands, we engineered murine T cells with two distinct NKG2D-based chimeric antigen receptors (CARs): (i) a fusion between the NKG2D receptor and the CD3ζ chain and (ii) a conventional second-generation CAR, where the extracellular domain of NKG2D was fused to CD28 and CD3ζ. To enhance the CAR surface expression, we also engineered T cells to coexpress DAP10. In vitro functionality and surface expression levels of all three CARs was greater in BALB/c T cells than C57BL/6 T cells, indicating strain-specific differences. Upon adoptive transfer of NKG2D-CAR-T cells into syngeneic animals, we observed significant clinical toxicity resulting in morbidity and mortality. The severity of these toxicities varied between the CAR configurations and paralleled their in vitro NKG2D surface expression. BALB/c mice were more sensitive to these toxicities than C57BL/6 mice, consistent with the higher in vitro functionality of BALB/c T cells. Treatment with cyclophosphamide prior to adoptive transfer exacerbated the toxicity. We conclude that while NKG2D ligands may be useful targets for immunotherapy, the pursuit of NKG2D-based CAR-T cell therapies should be undertaken with caution.
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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.