AUTHOR=Liang Juan , Fu Liang , Li Man , Chen Yuyuan , Wang Yi , Lin Yi , Zhang Hailin , Xu Yan , Qin Linxiu , Liu Juncai , Wang Weiyu , Hao Jianlei  , Liu Shuyan , Zhang Peize , Lin Li , Alnaggar Mohammed , Zhou Jie , Zhou Lin , Guo Huixin , Wang Zhaoqin , Liu Lei , Deng Guofang , Zhang Guoliang , Wu Yangzhe , Yin Zhinan 

TITLE=Allogeneic Vγ9Vδ2 T-Cell Therapy Promotes Pulmonary Lesion Repair: An Open-Label, Single-Arm Pilot Study in Patients With Multidrug-Resistant Tuberculosis

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.756495

DOI=10.3389/fimmu.2021.756495

ISSN=1664-3224

ABSTRACT=<p>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 × 10<sup>8</sup>) 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 <italic>Mycobacterium tuberculosis</italic> 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 <italic>M. tuberculosis</italic> load <italic>in vivo</italic>, 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.</p><sec><title>Clinical Trial Registration</title><p>(<uri xlink:href="https://clinicaltrials.gov/ct2/results?cond=&amp;term=NCT03575299&amp;cntry=&amp;state=&amp;city=&amp;dist=" xmlns:xlink="http://www.w3.org/1999/xlink">https://clinicaltrials.gov/ct2/results?cond=&amp;term=NCT03575299&amp;cntry=&amp;state=&amp;city=&amp;dist=</uri>) ( NCT03575299).</p></sec>