ArticleJCI insight2020
A rational mouse model to detect on-target, off-tumor CAR T cell toxicity.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 3 of them syntheses that pooled it.
What it found
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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
69 citing papers in PubMed, 3 syntheses or guidelines pooled it, 94 citations in OpenAlex.
- The synergistic immunotherapeutic impact of engineered CAR-T cells with PD-1 blockade in lymphomas and solid tumors: a systematic review.Frontiers in immunology · 2024Pooled it
- Prophylactic use of interleukin 6 monoclonal antibody can reduce CRS response of CAR-T cell therapy.Frontiers in medicine · 2023Pooled it
- A Systematic Review of the Efforts and Hindrances of Modeling and Simulation of CAR T-cell Therapy.The AAPS journal · 2021Pooled it
- Multi-dimensional orchestration of binders for improved CAR-T immunotherapy.Cancer letters · 2026Review
- Programmable CAR and antigen pairing for solid tumor immunotherapy.Molecular therapy. Oncology · 2026Article
- Engineering the next generation of cellular therapies for solid tumors: multi-specific armored CARs and TME reprogramming strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Deep learning for optoacoustic imaging of reversibly switchable proteins: training and performance testing using simulated multispectral optoacoustic tomography images.Journal of biomedical optics · 2026Article
- Recognition of ErbB Family Dimers by the EGF-like Domain of NRG1alpha and Beta: Implications for Ligand-Based CAR Therapy.International journal of molecular sciences · 2026Article
- Review
- Spatial Regulation of CAR Signaling Enables Logic-Gated Activity.bioRxiv : the preprint server for biology · 2026Article
- In vivo CAR-T therapy: from molecular design to precision delivery.Journal of nanobiotechnology · 2026Review
- Synergistic Antitumor Efficacy of Radiofrequency Ablation Combined With TROP2-CAR-T Cells in a Xenograft Mouse Model of Lung Adenocarcinoma.Thoracic cancer · 2026Article
- Engineering programmable CAR and antigen pairing via drug-gated light activation.Nature communications · 2026Article
- Ferroptosis, pyroptosis, and necroptosis in melanoma: regulatory cell death pathways and their implications for immunotherapy.Frontiers in oncology · 2026Review
- Engineering a juxtamembrane-targeting CAR T-cell against mesothelin: a novel binder resilient to shed antigen for enhanced efficacy against ovarian and pancreatic cancer.Frontiers in immunology · 2026Article
- Chimeric antigen receptor macrophages therapy for glioblastoma: challenges and opportunities from preclinical evidence to clinical translation.Frontiers in immunology · 2026Review
- Preclinical development and selection of nanobody-based CAR-T cells targeting HER2-positive solid tumors.Molecular therapy. Oncology · 2025Article
- Generation Using Phage-Display of pH-Dependent Antibodies Against the Tumor-Associated Antigen AXL.Antibodies (Basel, Switzerland) · 2025Article
- Antitumor Activities by a Humanized Cancer-Specific Anti-Podoplanin Monoclonal Antibody humPMab-117 Against Human Tumors.Cancer science · 2025Article
- Harnessing Macrophages in Cancer Therapy: from Immune Modulators to Therapeutic Targets.International journal of biological sciences · 2025Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Off-tumor targeting of human antigens is difficult to predict in preclinical animal studies and can lead to serious adverse effects in patients. To address this, we developed a mouse model with stable and tunable human Her2 (hHer2) expression on normal hepatic tissue and compared toxicity between affinity-tuned Her2 chimeric antigen receptor T cells (CARTs). In mice with hHer2-high livers, both the high-affinity (HA) and low-affinity (LA) CARTs caused lethal liver damage due to immunotoxicity. In mice with hHer2-low livers, LA-CARTs exhibited less liver damage and lower systemic levels of IFN-γ than HA-CARTs. We then compared affinity-tuned CARTs for their ability to control a hHer2-positive tumor xenograft in our model. Surprisingly, the LA-CARTs outperformed the HA-CARTs with superior antitumor efficacy in vivo. We hypothesized that this was due, in part, to T cell trafficking differences between LA and HA-CARTs and found that the LA-CARTs migrated out of the liver and infiltrated the tumor sooner than the HA-CARTs. These findings highlight the importance of T cell targeting in reducing toxicity of normal tissue and also in preventing off-tumor sequestration of CARTs, which reduces their therapeutic potency. Our model may be useful to evaluate various CARTs that have conditional expression of more than 1 single-chain variable fragment (scFv).
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What OpenQuestion holds
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.