دورية أكاديمية
Rapid generation of a mouse model for evaluating on-target normal tissue toxicity of human CAR-T cells using replication-defective recombinant adenovirus
| العنوان: | Rapid generation of a mouse model for evaluating on-target normal tissue toxicity of human CAR-T cells using replication-defective recombinant adenovirus |
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| المؤلفون: | Qibin Liao, Zhuoqun Liu, Cuisong Zhu, Huan He, Meiqi Feng, Lang Jiang, Xiangqing Ding, Rongxun Sun, Xiaoyan Zhang, Jianqing Xu |
| المصدر: | Journal of Advanced Research, Vol 47, Iss , Pp 163-171 (2023) |
| بيانات النشر: | Elsevier, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Medicine (General) LCC:Science (General) |
| مصطلحات موضوعية: | CAR-T, On-target off-tumor toxicity, Normal tissue, Animal model, Adenovirus, Medicine (General), R5-920, Science (General), Q1-390 |
| الوصف: | Introduction: The on-target off-tumor toxicity of chimeric antigen receptor-engineered T cells (CAR-T) might lead to fatal side effects in cancer patients, which remains as a major obstacle to the clinical application of CAR-T immunotherapy. The off-tumor on-target normal tissue toxicity of CAR-T cells needs to be evaluated in preclinical studies using rational animal models. Objectives: We aim to develop a rational animal model for assessing the off-tumor on-target normal tissue toxicity of various CAR-T cell designs quickly. Methods: We used a recombinant adenovirus type 5 carrying human HER2/ERBB2 (Ad5-HER2) or CD47 gene (Ad5-CD47) to rapidly generate a mouse model with tunable human antigen expression on normal liver tissue to determine immunotoxicity of traditional CAR-T and hypoxia-response CAR-T cells in vivo. Results: The obvious liver damage and lymphocyte infiltration were not observed in mice with human antigen-high livers 8 days post-infection. Interestingly, the lethal liver damage, systemic cytokine release and CAR-T cells infiltration in liver were only observed in mice that received traditional CAR-T cells, but not in hypoxia-response CAR-T cells. Conclusion: Adenovirus-based expression of target antigen in normal mouse tissue may be a useful method for assessing on-target CAR-T cell toxicity in normal tissues, especially various CAR-T cell designs that have the potency of conditional regulation in tumor microenvironment (TME). |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2090-1232 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2090123222001898; https://doaj.org/toc/2090-1232 |
| DOI: | 10.1016/j.jare.2022.08.008 |
| URL الوصول: | https://doaj.org/article/e7f3ea80a48e436eaed7cc7ba82f1d46 |
| رقم الأكسشن: | edsdoj.7f3ea80a48e436eaed7cc7ba82f1d46 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20901232 |
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| DOI: | 10.1016/j.jare.2022.08.008 |