ArticlePloS one2012
Redirecting T cells to Ewing's sarcoma family of tumors by a chimeric NKG2D receptor expressed by lentiviral transduction or mRNA transfection.
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 80 papers.
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Who cites it
80 citing papers in PubMed, 105 citations in OpenAlex.
- Harnessing the NKG2D immune surveillance pathway using engineered T-cells for the treatment of human disease.Human vaccines & immunotherapeutics · 2026Review
- Application of CAR-T cell therapy in orthopedics: From bone malignancies to non-malignant musculoskeletal disorders.Journal of orthopaedic translation · 2026Review
- Advances inMolecular therapy. Nucleic acids · 2026Review
- Immunotherapy: the Mega Weapon to Cure Cancer.Journal of family & reproductive health · 2026Review
- Messenger RNA therapy in bone and joint diseases: Rationale, delivery systems, and applications.Biomaterials translational · 2026Article
- Designs of NKG2D-based immunotherapeutics for cancer.Frontiers in immunology · 2025Review
- Solid tumor immunotherapy using NKG2D-based adaptor CAR T cells.Cell reports. Medicine · 2024Article
- 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
- Overall review of curative impact and barriers of CAR-T cells in osteosarcoma.EXCLI journal · 2024Review
- Recruiting In Vitro Transcribed mRNA against Cancer Immunotherapy: A Contemporary Appraisal of the Current Landscape.Current issues in molecular biology · 2023Review
- RNA-Based Therapeutic Technology.International journal of molecular sciences · 2023Review
- SWI/SNF Complex Alterations in Tumors with Rhabdoid Features: Novel Therapeutic Approaches and Opportunities for Adoptive Cell Therapy.International journal of molecular sciences · 2023Review
- CX3CR1 deficiency-induced TIL tumor restriction as a novel addition for CAR-T design in solid malignancies.iScience · 2023Article
- Current Landscape of Immunotherapy for Advanced Sarcoma.Cancers · 2023Review
- Chimeric antigen receptor-engineered NK cells: new weapons of cancer immunotherapy with great potential.Experimental hematology & oncology · 2022Review
- Immunotherapeutic targeting of activating natural killer cell receptors and their ligands in cancer.Clinical and experimental immunology · 2022Review
- The antigen-binding moiety in the driver's seat of CARs.Medicinal research reviews · 2022Review
- Suppression of 4.1R enhances the potency of NKG2D-CAR T cells against pancreatic carcinoma via activating ERK signaling pathway.Oncogenesis · 2021Article
- Chimeric Antigen Receptor T cell Therapy and the Immunosuppressive Tumor Microenvironment in Pediatric Sarcoma.Cancers · 2021Review
- Manufacturing NKG2D CAR-T cells with piggyBac transposon vectors and K562 artificial antigen-presenting cells.Molecular therapy. Methods & clinical development · 2021Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We explored the possibility to target Ewing's sarcoma family of tumors (ESFT) by redirecting T cells. To this aim, we considered NKG2D-ligands (NKG2D-Ls) as possible target antigens. Detailed analysis of the expression of MICA, MICB, ULBP-1, -2, and -3 in fourteen ESFT cell lines revealed consistent expression of at least one NKG2D-L. Thus, for redirecting T cells, we fused a CD3ζ/CD28-derived signaling domain to the ectodomain of NKG2D, however, opposite transmembrane orientation of this signaling domain and NKG2D required inverse orientation fusion of either of them. We hypothesized that the particularly located C-terminus of the NKG2D ectodomain should allow reengineering of the membrane anchoring from a native N-terminal to an artificial C-terminal linkage. Indeed, the resulting chimeric NKG2D receptor (chNKG2D) was functional and efficiently mediated ESFT cell death triggered by activated T cells. Notably, ESFT cells with even low NKG2D-L expression were killed by CD8(pos) and also CD4(pos) cells. Both, mRNA transfection and lentiviral transduction resulted in high level surface expression of chNKG2D. However, upon target-cell recognition receptor surface levels were maintained by tranfected RNA only during the first couple of hours after transfection. Later, target-cell contact resulted in strong and irreversible receptor down-modulation, whereas lentivirally mediated expression of chNKG2D remained constant under these conditions. Together, our study defines NKG2D-Ls as targets for a CAR-mediated T cell based immunotherapy of ESFT. A comparison of two different methods of gene transfer reveals strong differences in the susceptibility to ligand-induced receptor down-modulation with possible implications for the applicability of RNA transfection.
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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.