ArticleJournal of immunotherapy (Hagerstown, Md. : 1997)2016
Redirecting T-Cell Specificity to EGFR Using mRNA to Self-limit Expression of Chimeric Antigen Receptor.
Article in Journal of immunotherapy (Hagerstown, Md. : 1997), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Advances inMolecular therapy. Nucleic acids · 2026Review
- Self-amplifying RNA-based CAR T cell therapy with enhanced duration and multi-genic logic functions.bioRxiv : the preprint server for biology · 2026Article
- Preclinical efficacy of multi-targeting mRNA-based CAR T cell therapy in resection models of glioblastoma.Molecular therapy. Nucleic acids · 2025Article
- mRNA-engineered T lymphocytes secreting bispecific T cell engagers with therapeutic potential in solid tumors.Frontiers in immunology · 2025Article
- Oxidized mRNA Lipid Nanoparticles forAdvanced functional materials · 2024Article
- RNA-Based Therapeutic Technology.International journal of molecular sciences · 2023Review
- Advances in Development of mRNA-Based Therapeutics.Current topics in microbiology and immunology · 2022Article
- mRNA Therapeutic Modalities Design, Formulation and Manufacturing under Pharma 4.0 Principles.Biomedicines · 2021Review
- Clinical and immunological effects of mRNA vaccines in malignant diseases.Molecular cancer · 2021Review
- Recognition of Tumor-Associated Antigens and Immune Subtypes in Glioma for mRNA Vaccine Development.Frontiers in immunology · 2021Article
- [Immunotherapies for the treatment of chronic hepatitis B virus infections-an overview with a focus on CAR T cells].Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz · 2020Review
- RNA-electroporated T cells for cancer immunotherapy.Oncoimmunology · 2020Review
- In Vitro-Transcribed mRNA Chimeric Antigen Receptor T Cell (IVT mRNA CAR T) Therapy in Hematologic and Solid Tumor Management: A Preclinical Update.International journal of molecular sciences · 2020Review
- CAR T cells and checkpoint inhibition for the treatment of glioblastoma.Expert opinion on biological therapy · 2020Review
- Review
- Preclinical Activity of Embryonic Annexin A2-Specific Chimeric Antigen Receptor T Cells Against Ovarian Cancer.International journal of molecular sciences · 2020Article
- Glycoengineering of chimeric antigen receptor (CAR) T-cells to enforce E-selectin binding.The Journal of biological chemistry · 2019Article
- Review
- RNA-Modified T Cells Mediate Effective Delivery of Immunomodulatory Cytokines to Brain Tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- The Emerging Role of In Vitro-Transcribed mRNA in Adoptive T Cell Immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Potential for on-target, but off-tissue toxicity limits therapeutic application of genetically modified T cells constitutively expressing chimeric antigen receptors (CARs) from tumor-associated antigens expressed in normal tissue, such as epidermal growth factor receptor (EGFR). Curtailing expression of CAR through modification of T cells by in vitro-transcribed mRNA species is one strategy to mitigate such toxicity. We evaluated expression of an EGFR-specific CAR coded from introduced mRNA in human T cells numerically expanded ex vivo to clinically significant numbers through coculture with activating and propagating cells (AaPC) derived from K562 preloaded with anti-CD3 antibody. The density of AaPC could be adjusted to affect phenotype of T cells such that reduced ratio of AaPC resulted in higher proportion of CD8 and central memory T cells that were more conducive to electrotransfer of mRNA than T cells expanded with high ratios of AaPC. RNA-modified CAR T cells produced less cytokine, but demonstrated similar cytolytic capacity as DNA-modified CAR T cells in response to EGFR-expressing glioblastoma cells. Expression of CAR by mRNA transfer was transient and accelerated by stimulation with cytokine and antigen. Loss of CAR abrogated T-cell function in response to tumor and normal cells expressing EGFR. We describe a clinically applicable method to propagate and modify T cells to transiently express EGFR-specific CAR to target EGFR-expressing tumor cells that may be used to limit on-target, off-tissue toxicity to normal tissue.
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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.