Cell Discovery (May 2024)

Efficacy and safety of novel multifunctional M10 CAR-T cells in HIV-1-infected patients: a phase I, multicenter, single-arm, open-label study

  • 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

DOI
https://doi.org/10.1038/s41421-024-00658-z
Journal volume & issue
Vol. 10, no. 1
pp. 1 – 16

Abstract

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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.