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The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity
CAR T-cell therapy is well tolerated and effective in patients with Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). However, even second- generation anti-CD30 CAR T-cells with CD28 (28z) costimulatory domains failed to achieve the desired rate of complete responses. In the present s...
| Autores principales: | , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2022
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213494/ https://www.ncbi.nlm.nih.gov/pubmed/35729339 http://dx.doi.org/10.1038/s41598-022-14523-0 |
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| author | Zhang, Shangkun Gu, Chaojiang Huang, Lifang Wu, Han Shi, Jiangzhou Zhang, Zijian Zhou, Yong Zhou, Jingjiao Gao, Yang Liu, Jiaxing Leng, Yingqi Liu, Xiyu Zhang, Qinxing Huang, Liang Tong, Xiqin Young, Ken H. Li, Jiapeng Zhu, Haichuan Zhang, Tongcun |
| author_facet | Zhang, Shangkun Gu, Chaojiang Huang, Lifang Wu, Han Shi, Jiangzhou Zhang, Zijian Zhou, Yong Zhou, Jingjiao Gao, Yang Liu, Jiaxing Leng, Yingqi Liu, Xiyu Zhang, Qinxing Huang, Liang Tong, Xiqin Young, Ken H. Li, Jiapeng Zhu, Haichuan Zhang, Tongcun |
| author_sort | Zhang, Shangkun |
| collection | PubMed |
| description | CAR T-cell therapy is well tolerated and effective in patients with Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). However, even second- generation anti-CD30 CAR T-cells with CD28 (28z) costimulatory domains failed to achieve the desired rate of complete responses. In the present study, we developed second-generation (CD28z) and third-generation (CD28BBz) CAR T-cells targeting CD30 and investigated their efficacy in vitro and in vivo. Both of CD28z and CD28BBz anti-CD30 CAR T cells were similar regarding amplification, T cell subsets distribution, T cell activity, effector/memory and exhaustion. However, we found that the 28BBz anti-CD30 CAR T-cells persist long-term, specifically homing to the tumor and mediating powerful antitumor activity in tumor xenograft models. Subsequently, we also demonstrated that the third generation anti-CD30 CAR T-cells have miner side effects or potential risks of tumorigenesis. Thus, anti-CD30 CAR T-cells represent a safe and effective treatment for Hodgkin lymphoma. |
| format | Online Article Text |
| id | pubmed-9213494 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2022 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-92134942022-06-23 The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity Zhang, Shangkun Gu, Chaojiang Huang, Lifang Wu, Han Shi, Jiangzhou Zhang, Zijian Zhou, Yong Zhou, Jingjiao Gao, Yang Liu, Jiaxing Leng, Yingqi Liu, Xiyu Zhang, Qinxing Huang, Liang Tong, Xiqin Young, Ken H. Li, Jiapeng Zhu, Haichuan Zhang, Tongcun Sci Rep Article CAR T-cell therapy is well tolerated and effective in patients with Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). However, even second- generation anti-CD30 CAR T-cells with CD28 (28z) costimulatory domains failed to achieve the desired rate of complete responses. In the present study, we developed second-generation (CD28z) and third-generation (CD28BBz) CAR T-cells targeting CD30 and investigated their efficacy in vitro and in vivo. Both of CD28z and CD28BBz anti-CD30 CAR T cells were similar regarding amplification, T cell subsets distribution, T cell activity, effector/memory and exhaustion. However, we found that the 28BBz anti-CD30 CAR T-cells persist long-term, specifically homing to the tumor and mediating powerful antitumor activity in tumor xenograft models. Subsequently, we also demonstrated that the third generation anti-CD30 CAR T-cells have miner side effects or potential risks of tumorigenesis. Thus, anti-CD30 CAR T-cells represent a safe and effective treatment for Hodgkin lymphoma. Nature Publishing Group UK 2022-06-21 /pmc/articles/PMC9213494/ /pubmed/35729339 http://dx.doi.org/10.1038/s41598-022-14523-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article Zhang, Shangkun Gu, Chaojiang Huang, Lifang Wu, Han Shi, Jiangzhou Zhang, Zijian Zhou, Yong Zhou, Jingjiao Gao, Yang Liu, Jiaxing Leng, Yingqi Liu, Xiyu Zhang, Qinxing Huang, Liang Tong, Xiqin Young, Ken H. Li, Jiapeng Zhu, Haichuan Zhang, Tongcun The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity |
| title | The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity |
| title_full | The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity |
| title_fullStr | The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity |
| title_full_unstemmed | The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity |
| title_short | The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity |
| title_sort | third-generation anti-cd30 car t-cells specifically homing to the tumor and mediating powerful antitumor activity |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213494/ https://www.ncbi.nlm.nih.gov/pubmed/35729339 http://dx.doi.org/10.1038/s41598-022-14523-0 |
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