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Pharmacokinetic and pharmacodynamic studies of CD19 CAR T cell in human leukaemic xenograft models with dual‐modality imaging
In recent years, chimeric antigen receptor T (CAR T)‐cell therapy has shown great potential in treating haematologic disease, but no breakthrough has been achieved in solid tumours. In order to clarify the antitumour mechanism of CAR T cell in solid tumours, the pharmacokinetic (PK) and pharmacodyna...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335694/ https://www.ncbi.nlm.nih.gov/pubmed/34245101 http://dx.doi.org/10.1111/jcmm.16776 |
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author | Wu, Qiong Wang, Yan Wang, Xinyu Liang, Ningxia Liu, Jingjing Pan, Donghui Xu, Yuping Wang, Lizhen Yan, Junjie Wang, Guangji Miao, Liyan Yang, Min |
author_facet | Wu, Qiong Wang, Yan Wang, Xinyu Liang, Ningxia Liu, Jingjing Pan, Donghui Xu, Yuping Wang, Lizhen Yan, Junjie Wang, Guangji Miao, Liyan Yang, Min |
author_sort | Wu, Qiong |
collection | PubMed |
description | In recent years, chimeric antigen receptor T (CAR T)‐cell therapy has shown great potential in treating haematologic disease, but no breakthrough has been achieved in solid tumours. In order to clarify the antitumour mechanism of CAR T cell in solid tumours, the pharmacokinetic (PK) and pharmacodynamic (PD) investigations of CD19 CAR T cell were performed in human leukaemic xenograft mouse models. For PK investigation, we radiolabelled CD19 CAR T cell with (89)Zr and used PET imaging in the CD19‐positive and the CD19‐negative K562‐luc animal models. For PD evaluation, optical imaging, tumour volume measurement and DNA copy‐number detection were performed. Unfortunately, the qPCR results of the DNA copy number in the blood were below the detection limit. The tumour‐specific uptake was higher in the CD19‐positive model than in the CD19‐negative model, and this was consistent with the PD results. The preliminary PK and PD studies of CD19 CAR T cell in solid tumours are instructive. Considering the less efficiency of CAR T‐cell therapy of solid tumours with the limited number of CAR T cells entering the interior of solid tumours, this study is suggestive for the subsequent CAR T‐cell design and evaluation of solid tumour therapy. |
format | Online Article Text |
id | pubmed-8335694 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83356942021-08-09 Pharmacokinetic and pharmacodynamic studies of CD19 CAR T cell in human leukaemic xenograft models with dual‐modality imaging Wu, Qiong Wang, Yan Wang, Xinyu Liang, Ningxia Liu, Jingjing Pan, Donghui Xu, Yuping Wang, Lizhen Yan, Junjie Wang, Guangji Miao, Liyan Yang, Min J Cell Mol Med Original Articles In recent years, chimeric antigen receptor T (CAR T)‐cell therapy has shown great potential in treating haematologic disease, but no breakthrough has been achieved in solid tumours. In order to clarify the antitumour mechanism of CAR T cell in solid tumours, the pharmacokinetic (PK) and pharmacodynamic (PD) investigations of CD19 CAR T cell were performed in human leukaemic xenograft mouse models. For PK investigation, we radiolabelled CD19 CAR T cell with (89)Zr and used PET imaging in the CD19‐positive and the CD19‐negative K562‐luc animal models. For PD evaluation, optical imaging, tumour volume measurement and DNA copy‐number detection were performed. Unfortunately, the qPCR results of the DNA copy number in the blood were below the detection limit. The tumour‐specific uptake was higher in the CD19‐positive model than in the CD19‐negative model, and this was consistent with the PD results. The preliminary PK and PD studies of CD19 CAR T cell in solid tumours are instructive. Considering the less efficiency of CAR T‐cell therapy of solid tumours with the limited number of CAR T cells entering the interior of solid tumours, this study is suggestive for the subsequent CAR T‐cell design and evaluation of solid tumour therapy. John Wiley and Sons Inc. 2021-07-09 2021-08 /pmc/articles/PMC8335694/ /pubmed/34245101 http://dx.doi.org/10.1111/jcmm.16776 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Wu, Qiong Wang, Yan Wang, Xinyu Liang, Ningxia Liu, Jingjing Pan, Donghui Xu, Yuping Wang, Lizhen Yan, Junjie Wang, Guangji Miao, Liyan Yang, Min Pharmacokinetic and pharmacodynamic studies of CD19 CAR T cell in human leukaemic xenograft models with dual‐modality imaging |
title | Pharmacokinetic and pharmacodynamic studies of CD19 CAR T cell in human leukaemic xenograft models with dual‐modality imaging |
title_full | Pharmacokinetic and pharmacodynamic studies of CD19 CAR T cell in human leukaemic xenograft models with dual‐modality imaging |
title_fullStr | Pharmacokinetic and pharmacodynamic studies of CD19 CAR T cell in human leukaemic xenograft models with dual‐modality imaging |
title_full_unstemmed | Pharmacokinetic and pharmacodynamic studies of CD19 CAR T cell in human leukaemic xenograft models with dual‐modality imaging |
title_short | Pharmacokinetic and pharmacodynamic studies of CD19 CAR T cell in human leukaemic xenograft models with dual‐modality imaging |
title_sort | pharmacokinetic and pharmacodynamic studies of cd19 car t cell in human leukaemic xenograft models with dual‐modality imaging |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335694/ https://www.ncbi.nlm.nih.gov/pubmed/34245101 http://dx.doi.org/10.1111/jcmm.16776 |
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