Allogeneic Vγ9Vδ2 T-Cell Therapy Promotes Pulmonary Lesion Repair: An Open-Label, Single-Arm Pilot Study in Patients With Multidrug-Resistant Tuberculosis.
Allogeneic Vγ9Vδ2 T-Cell Therapy Promotes Pulmonary Lesion Repair: An Open-Label, Single-Arm Pilot Study in Patients With Multidrug-Resistant Tuberculosis.
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同种异体 Vγ9Vγ2 T 细胞疗法促进肺部病变修复：一项针对耐多药结核病患者的开放标签、单臂试点研究
DOI：
10.3389/fimmu.2021.756495
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发表时间：
2021
影响因子：
7.3
通讯作者：
Yin Z
中科院分区：
文献类型：
--
作者：
Liang J;Fu L;Li M;Chen Y;Wang Y;Lin Y;Zhang H;Xu Y;Qin L;Liu J;Wang W;Hao J;Liu S;Zhang P;Lin L;Alnaggar M;Zhou J;Zhou L;Guo H;Wang Z;Liu L;Deng G;Zhang G;Wu Y;Yin Z
世卫组织的《2020年全球结核病报告》将结核病列为全球主要死亡原因之一。现有的抗结核治疗战略远远不足以实现2035年结束结核病战略的目标。因此，迫切需要新的抗TB治疗方案。在此，我们提出了一种基于同种异体Vγ9Vδ2 T细胞的免疫治疗策略，并在临床上评估了其在耐多药结核病（MDR-TB）患者中的安全性和有效性。在这项开放标签、单臂初步临床研究中招募了8名耐多药结核病患者。其中7例患者在所有治疗过程中接受了同种异体Vγ9Vδ2 T细胞治疗和抗TB药物辅助治疗。每2周输注1 × 108个细胞，每例患者进行12个疗程的细胞治疗，随访6个月，评价细胞治疗的安全性和有效性。第八名患者最初接受了四个疗程的细胞输注，随后接受了八个疗程的细胞治疗加抗MDR-TB药物。进行临床检查，包括临床反应、血常规和生化指标、胸部CT成像、免疫细胞表面标志物、体重和痰结核分枝杆菌检测。我们的研究表明，同种异体Vγ 9 V δ2 T细胞对于结核病治疗在临床上是安全的。这些细胞在多个方面显示出临床功效，包括促进肺部病变的修复，部分提高宿主免疫力，以及减轻M.结核病负荷在体内，无论其应用在存在或不存在抗结核药物。这项初步研究开辟了抗结核治疗的新途径，并显示同种异体Vγ9Vδ2 T细胞是开发用于结核免疫治疗的新型细胞药物的有希望的候选者。（）（NCT 03575299）。
The WHO’s “Global tuberculosis report 2020” lists tuberculosis (TB) as one of the leading causes of death globally. Existing anti-TB therapy strategies are far from adequate to meet the End TB Strategy goals set for 2035. Therefore, novel anti-TB therapy protocols are urgently needed. Here, we proposed an allogeneic Vγ9Vδ2 T-cell-based immunotherapy strategy and clinically evaluated its safety and efficacy in patients with multidrug-resistant TB (MDR-TB). Eight patients with MDR-TB were recruited in this open-label, single-arm pilot clinical study. Seven of these patients received allogeneic Vγ9Vδ2 T-cell therapy adjunct with anti-TB drugs in all therapy courses. Cells (1 × 108) were infused per treatment every 2 weeks, with 12 courses of cell therapy conducted for each patient, who were then followed up for 6 months to evaluate the safety and efficacy of cell therapy. The eighth patient initially received four courses of cell infusions, followed by eight courses of cell therapy plus anti-MDR-TB drugs. Clinical examinations, including clinical response, routine blood tests and biochemical indicators, chest CT imaging, immune cell surface markers, body weight, and sputum Mycobacterium tuberculosis testing, were conducted. Our study revealed that allogeneic Vγ9Vδ2 T cells are clinically safe for TB therapy. These cells exhibited clinical efficacy in multiple aspects, including promoting the repair of pulmonary lesions, partially improving host immunity, and alleviating M. tuberculosis load in vivo, regardless of their application in the presence or absence of anti-TB drugs. This pilot study opens a new avenue for anti-TB treatment and exhibits allogeneic Vγ9Vδ2 T cells as promising candidates for developing a novel cell drug for TB immunotherapy. () ( NCT03575299).