Transfer of autologous gene-modified T cells in HIV-infected patients with advanced immunodeficiency and drug-resistant virus
Transfer of autologous gene-modified T cells in HIV-infected patients with advanced immunodeficiency and drug-resistant virus
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DOI：
10.1038/mt.sj.6300124
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发表时间：
2007-05-01
影响因子：
12.4
通讯作者：
von Laer, Dorothee
中科院分区：
文献类型：
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作者：
van Lunzen, Jan;Glaunsinger, Tobias;von Laer, Dorothee
药物毒性和病毒耐药性限制了抗病毒药物治疗人类免疫缺陷病毒（HIV）感染的长期疗效。因此，需要探索替代疗法。我们测试了用表达HIV进入抑制肽（maC46）的逆转录病毒载体（M87o）转导的T淋巴细胞的输注。在抗逆转录病毒联合治疗期间，将基因修饰的自体T细胞输注到10名患有晚期疾病和多药耐药病毒的HIV感染患者中。T细胞输注耐受性良好，没有严重的副作用。输注后观察到CD4计数显著增加。1年随访结束时，所有患者的CD4计数仍在基线附近或高于基线。在1年的随访中，可以在外周血、淋巴结和骨髓中检测到基因修饰细胞，标记水平与细胞剂量相关。在前4个月内未观察到病毒载量的显著变化。7名患者中有4名改变了抗病毒药物治疗方案，血浆病毒载量显著下降。总之，基因修饰细胞的转移是安全的，导致持续的基因标记水平，并可能提高晚期疾病和多重耐药病毒的HIV感染患者的免疫能力。
Drug toxicity and viral resistance limit the long-term efficacy of antiviral drug treatment for human immunodeficiency virus (HIV) infection. Thus, alternative therapies need to be explored. We tested the infusion of T lymphocytes transduced with a retroviral vector (M87o) that expresses an HIV entry - inhibitory peptide (maC46). Gene-modified autologous T cells were infused into ten HIV-infected patients with advanced disease and multidrug-resistant virus during antiretroviral combination therapy. T-cell infusions were tolerated well, with no severe side effects. A significant increase of CD4 counts was observed after infusion. At the end of the 1-year follow-up, the CD4 counts of all patients were still around or above baseline. Gene-modified cells could be detected in peripheral blood, lymph nodes, and bone marrow throughout the 1-year follow-up, and marking levels correlated with the cell dose. No significant changes of viral load were observed during the first 4 months. Four of the seven patients who changed their antiviral drug regimen thereafter responded with a significant decline in plasma viral load. In conclusion, the transfer of gene-modified cells was safe, led to sustained levels of gene marking, and may improve immune competence in HIV-infected patients with advanced disease and multidrug-resistant virus.