ArticlePloS one2019
TEM8/ANTXR1-specific CAR T cells mediate toxicity in vivo.
Article in PloS one, 2019. 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
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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.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Hybrid bioinspired nanovescicles target tumor endothelial cells and regulate immuno-microenvironment for triple-negative breast cancer therapy.Journal of translational medicine · 2026Article
- Engineering CAR-T cells for solid tumors: overcoming antigenic, trafficking, and microenvironmental barriers.Frontiers in immunology · 2026Review
- Tumour-associated vasculature in T cell homing and immunity: opportunities for cancer therapy.Nature reviews. Immunology · 2025Review
- Advancements and challenges in CAR-T cell therapy for solid tumors: A comprehensive review of antigen targets, strategies, and future directions.Cancer cell international · 2025Review
- Combination strategies with PARP inhibitors in BRCA-mutated triple-negative breast cancer: overcoming resistance mechanisms.Oncogene · 2025Review
- Journey of CAR T‑cells: Emphasising the concepts and advancements in breast cancer (Review).International journal of oncology · 2023Review
- Review
- Targeting PD-1/PD-L1 in cancer immunotherapy: An effective strategy for treatment of triple-negative breast cancer (TNBC) patients.Genes & diseases · 2023Review
- Novel chimeric antigen receptor T cell-based immunotherapy: a perspective for triple-negative breast cancer.Frontiers in cell and developmental biology · 2023Review
- TEM8 Tri-specific Killer Engager binds both tumor and tumor stroma to specifically engage natural killer cell anti-tumor activity.Journal for immunotherapy of cancer · 2022Article
- Targeting the extra domain A of fibronectin for cancer therapy with CAR-T cells.Journal for immunotherapy of cancer · 2022Article
- COVID-19 and dys-regulation of pulmonary endothelium: implications for vascular remodeling.Cytokine & growth factor reviews · 2022Review
- CAR-T cell therapy in triple-negative breast cancer: Hunting the invisible devil.Frontiers in immunology · 2022Review
- Evolving role of seneca valley virus and its biomarker TEM8/ANTXR1 in cancer therapeutics.Frontiers in molecular biosciences · 2022Review
- Advances in CAR-T Cell Genetic Engineering Strategies to Overcome Hurdles in Solid Tumors Treatment.Frontiers in immunology · 2022Review
- Progress and Prospect of Immunotherapy for Triple-Negative Breast Cancer.Frontiers in oncology · 2022Review
- Deep Membrane Proteome Profiling Reveals Overexpression of Prostate-Specific Membrane Antigen (PSMA) in High-Risk Human Paraganglioma and Pheochromocytoma, Suggesting New Theranostic Opportunity.Molecules (Basel, Switzerland) · 2021Article
- Novel antigens of CAR T cell therapy: New roads; old destination.Translational oncology · 2021Review
- Enhancing CAR-T cell efficacy in solid tumors by targeting the tumor microenvironment.Cellular & molecular immunology · 2021Review
- Antitumor Effects of CAR T Cells Redirected to the EDB Splice Variant of Fibronectin.Cancer immunology research · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Engineering T-cells to express receptors specific for antigens present on tumour tissue is proving a highly effective treatment for some leukaemias. However, extending this to solid tumours requires antigens that can be safely and effectively targeted. TEM8, a marker overexpressed on the vasculature of some solid tumours, has been proposed as one such target. A recent report stated that T-cells engineered to express a TEM8-specific chimeric antigen receptor (CAR), when injected into mouse models of triple negative breast cancer, are both safe and effective in controlling tumour growth. Here we report contrasting data with a panel of TEM8-specific CAR-T-cells including one generated from the same antibody used in the other study. We found that the CAR-T-cells demonstrated clear TEM8-specific cytotoxic and cytokine release responses in vitro, but when injected into healthy C57BL6 and NSG mice they rapidly and selectively disappeared from the circulation and in most cases caused rapid toxicity. Infusing CAR-T-cells into a TEM8-knockout mouse indicated that selective loss of cells from the circulation was due to targeting of TEM8 in healthy tissues. Histological analysis of mice treated with a TEM8-specific CAR revealed evidence of inflammation in the lung and spleen with large collections of infiltrating neutrophils. Therefore our data raise concerns over potential on-target off-tumour toxicity with CARs targeting TEM8 and these should be considered carefully before embarking upon clinical trials with such agents.
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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.