| Autor: |
Yunyu Mao, Qibin Liao, Youwei Zhu, Mingyuan Bi, Jun Zou, Nairong Zheng, Lingyan Zhu, Chen Zhao, Qing Liu, Li Liu, Jun Chen, Ling Gu, Zhuoqun Liu, Xinghao Pan, Ying Xue, Meiqi Feng, Tianlei Ying, Pingyu Zhou, Zhanshuai Wu, Jian Xiao, Renfang Zhang, Jing Leng, Yongtao Sun, Xiaoyan Zhang, Jianqing Xu |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Cell Discovery, Vol 10, Iss 1, Pp 1-16 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2056-5968 |
| DOI: |
10.1038/s41421-024-00658-z |
| Popis: |
Abstract Chimeric antigen receptor T (CAR-T) cells have been proposed for HIV-1 treatment but have not yet demonstrated desirable therapeutic efficacy. Here, we report newly developed anti-HIV-1 CAR-T cells armed with endogenic broadly neutralizing antibodies (bNAbs) and the follicle-homing receptor CXCR5, termed M10 cells. M10 cells were designed to exercise three-fold biological functions, including broad cytotoxic effects on HIV-infected cells, neutralization of cell-free viruses produced after latency reversal, and B-cell follicle homing. After demonstrating the three-fold biological activities, M10 cells were administered to treat 18 HIV-1 patients via a regimen of two allogenic M10 cell infusions with an interval of 30 days, with each M10 cell infusion followed by two chidamide stimulations for HIV-1 reservoir activation. Consequently, 74.3% of M10 cell infusions resulted in significant suppression of viral rebound, with viral loads declining by an average of 67.1%, and 10 patients showed persistently reduced cell-associated HIV-1 RNA levels (average decrease of 1.15 log10) over the 150-day observation period. M10 cells were also found to impose selective pressure on the latent viral reservoir. No significant treatment-related adverse effects were observed. Overall, our study supported the potential of M10 CAR-T cells as a novel, safe, and effective therapeutic option for the functional cure of HIV-1/AIDS. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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