ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
T Cells Expressing NKG2D CAR with a DAP12 Signaling Domain Stimulate Lower Cytokine Production While Effective in Tumor Eradication.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. 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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Who cites it
44 citing papers in PubMed, 67 citations in OpenAlex.
- Sex determines the natural killer cell-mediated immunity against pancreatic cancer.Oncoimmunology · 2026Article
- Harnessing the NKG2D immune surveillance pathway using engineered T-cells for the treatment of human disease.Human vaccines & immunotherapeutics · 2026Review
- A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Reprogramming Antitumor Immunity: NK Cell Strategies to Navigate the Immunosuppressive Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Targeting the NKG2D axis in head and neck squamous cell carcinoma: from molecular insights to clinical applications.Cancer cell international · 2026Review
- NKG2D CAR-T cells for solid tumor immunotherapy: advances, challenges, and future directions.Frontiers in immunology · 2026Review
- Nanoparticle-based strategy in CAR-T cell immunotherapy: challenges, implications, and perspectives.Molecular cancer · 2025Review
- Synthetic NKG2D receptor (SNR) armored CAR-T cells overcome antigen heterogeneity of solid tumor.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Library-based single-cell analysis of CAR signaling reveals drivers of in vivo persistence.Cell systems · 2025Article
- Novel mRNA-Engineered Fully Human CAR-T Cells Targeting AXL in Solid Tumors.Biomedicines · 2025Article
- A chimeric antigen receptor tailored to integrate complementary activation signals potentiates the antitumor activity of NK cells.Journal of experimental & clinical cancer research : CR · 2025Article
- Pooled screening for CAR function identifies novel IL-13Rα2-targeted CARs for treatment of glioblastoma.Journal for immunotherapy of cancer · 2025Article
- Enhancing CAR T-Cell Function with Domains of Innate Immunity Sensors.International journal of molecular sciences · 2025Review
- Designs of NKG2D-based immunotherapeutics for cancer.Frontiers in immunology · 2025Review
- Leveraging innate immune signals in CD8+ T cells to boost antitumor immunity.Frontiers in immunology · 2025Review
- CAR-γδ T cells: a new paradigm of programmable innate immune sentinels and their systemic applications in cancer and beyond.Frontiers in immunology · 2025Review
- Solid tumor immunotherapy using NKG2D-based adaptor CAR T cells.Cell reports. Medicine · 2024Article
- Advances in CAR-T therapy for central nervous system tumors.Biomarker research · 2024Review
- Beyond CAR-T: The rise of CAR-NK cell therapy in asthma immunotherapy.Journal of translational medicine · 2024Review
- Poliovirus receptor-based chimeric antigen receptor T cells combined with NK-92 cells exert potent activity against glioblastoma.Journal of the National Cancer Institute · 2024Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytokine-related toxicity associated with the use of highly active chimeric antigen receptor T cells (CAR-T cells) is a significant clinical problem. By fusing the natural killer group 2D (NKG2D) ectodomain to 4-1BB and the DAP12 cytoplasmic domain containing only one immunoreceptor tyrosine-based activation motif, we have developed a 2nd-generation (2nd-Gen) NKG2D CAR for stable expression in human T cells. When compared to T cells modified with NKG2D CAR containing the commonly used CD3ζ activation domain, T cells expressing the NKG2D-DAP12 CAR stimulated lower level release of interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin (IL)-2 during tumor cell lysis and their proliferative activity was lower upon repeated antigen stimulation, although no difference between the two CARs was observed in mediating in vitro tumor cell lysis. In tumor-bearing NSG mice, both types of CAR-T cells displayed similar anti-tumor activity, being able to completely eradicate established solid tumor xenografts. However, treatment with the NKG2D-CD3ζ CAR-T cells led to the death of most mice from xenogeneic graft versus host disease starting 30 days post-CAR-T cell injection, which was associated with a higher level of cytokine release, whereas all the mice treated with the NKG2D-DAP12 CAR-T cells survived well. Thus, the incorporation of the DAP12 activation domain in a CAR design may possibly provide a potential clinical advantage in mitigating the risk of cytokine release syndrome (CRS).
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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.