van Lunzen Jan, Glaunsinger Tobias, Stahmer Ingrid, von Baehr Volker, Baum Christopher, Schilz Andrea, Kuehlcke Klaus, Naundorf Sonja, Martinius Holger, Hermann Felix, Giroglou Tsanan, Newrzela Sebastian, Müller Ingrid, Brauer Francis, Brandenburg Gunda, Alexandrov Alexander, von Laer Dorothee
Infectious Diseases Unit, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Mol Ther. 2007 May;15(5):1024-33. doi: 10.1038/mt.sj.6300124. Epub 2007 Mar 13.
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 anti-retroviral 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.
药物毒性和病毒耐药性限制了抗逆转录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。我们测试了输注用表达HIV进入抑制肽（maC46）的逆转录病毒载体（M87o）转导的T淋巴细胞。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例患有晚期疾病和多药耐药病毒的HIV感染患者体内。T细胞输注耐受性良好，无严重副作用。输注后观察到CD4细胞计数显著增加。在1年随访结束时，所有患者的CD4细胞计数仍在基线水平或以上。在整个1年随访期间，在外周血、淋巴结和骨髓中均可检测到基因修饰的细胞，标记水平与细胞剂量相关。在最初4个月内未观察到病毒载量有显著变化。此后改变抗逆转录病毒药物治疗方案的7例患者中有4例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，可导致基因标记持续存在，并可能改善患有晚期疾病和多药耐药病毒的HIV感染患者的免疫能力。
