ArticleClinical & translational immunology2021
A lymphodepleted non-human primate model for the assessment of acute on-target and off-tumor toxicity of human chimeric antigen receptor-T cells.
Article in Clinical & translational immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- mRNA-LNP vaccine providing antigen and co-stimulation in the tumor microenvironment enhances CAR T cell function (CART-Vac).Molecular therapy. Oncology · 2026Article
- In Vivo mRNA-Lipid Nanoparticle CAR-T Cell Engineering: Advances, Challenges, and Clinical Translation.Biomedicines · 2026Review
- Expression Profiles of Five Common Cancer Membrane Protein Antigens Collected for the Development of Cocktail CAR-T Cell Therapies Applicable to Most Solid Cancer Patients.International journal of molecular sciences · 2025Article
- In vivo tracking of ex-vivo-generatedMolecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Trial in progress: phase I study of non-viral gene-modified CAR-T cell therapy for malignant solid tumors expressing EPHB4 receptor (CARTiEr).Frontiers in oncology · 2025Article
- Evolving strategies for addressing CAR T-cell toxicities.Cancer metastasis reviews · 2024Review
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- Ligand-based, piggyBac-engineered CAR-T cells targeting EGFR are safe and effective against non-small cell lung cancers.Molecular therapy oncolytics · 2023Article
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- Applying a clinical lens to animal models of CAR-T cell therapies.Molecular therapy. Methods & clinical development · 2022Review
- Time to evolve: predicting engineered T cell-associated toxicity with next-generation models.Journal for immunotherapy of cancer · 2022Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesChimeric antigen receptor (CAR)-T cell therapy possesses the potential to cause unexpected on-target toxicities that may be life-threatening. Non-human primates (NHPs) share considerable structural homology and expression profiles of most proteins with humans and are therefore utilised as an animal model for non-clinical safety studies. We have developed a lymphodepleted NHP model by conditioning the animals with immunosuppressive chemotherapy designed to simulate clinical practice conditions, to induce transient mixed chimerism before the administration of human CAR-T cells redirected to target Ephrin type-B receptor 4 (EPHB4-CAR-T cells) to evaluate the toxicity of these cells.
methodsWe administered 60 mg m
resultsLymphodepletion was successfully achieved on day -1 before T-cell infusion and persisted over 7 days without severe organ toxicities. A single administration of human EPHB4-CAR-T cells did not induce overt organ toxicities, although EPHB4-CAR-T cells were activated
conclusionAlthough this NHP model is limited for the full evaluation of toxicity of human CAR-T cells and the conditioning protocol should be further optimised, this lymphodepleted NHP model could be used to assess acute on-target/off-tumor toxicities of CAR-T cells.
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