Allogeneic V gamma 9V delta 2 T-Cell Therapy Promotes Pulmonary Lesion Repair: An Open-Label, Single-Arm Pilot Study in Patients With Multidrug-Resistant Tuberculosis

Liang, Juan1,2,3; Fu, Liang2,4; Li, Man3,5; Chen, Yuyuan3; Wang, Yi2; Lin, Yi2; Zhang, Hailin2; Xu, Yan3; Qin, Linxiu2; Liu, Juncai2; Wang, Weiyu2; Hao, Jianlei3; Liu, Shuyan2; Zhang, Peize2; Lin, Li5; Alnaggar, Mohammed6; Zhou, Jie7; Zhou, Lin8; Guo, Huixin8; Wang, Zhaoqin2; Liu, Lei2; Deng, Guofang2; Zhang, Guoliang2; Wu, Yangzhe1,3; Yin, Zhinan1,3

2021-12-15

10.3389/fimmu.2021.756495

Frontiers in Immunology   影响因子和分区

1664-3224

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 V gamma 9V delta 2 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 V gamma 9V delta 2 T-cell therapy adjunct with anti-TB drugs in all therapy courses. Cells (1 x 10(8)) 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 V gamma 9V delta 2 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 V gamma 9V delta 2 T cells as promising candidates for developing a novel cell drug for TB immunotherapy.

multidrug-resistant TB allogeneic V gamma 9V delta 2 T cells immunotherapy immune regulation clinical study

SCI

英语

通讯

National Key Research and Development Plan["2019YFC0840602","2020YFA0907201"] ; Guangzhou Science and Technology Planning Project[201604020006] ; National Science and Technology Major Project for Control and Prevention of Major Infectious Diseases of China[2018ZX10715004] ; National Natural Science Foundation of China[81873958,81902031,82170009] ; Guangdong Scientific and Technological Foundation["2019B1515120041","2019B1515120067","2020B1111170014","2020A1515010977"] ; Shenzhen Scientific and Technological Project[KCXFZ202002011007083] ; Scientific Foundation of Shenzhen Municipal Health Commission[SZLY2018017] ; Sanming Project of Medicine in Shenzhen[SZSM201911009] ; "Dengfeng Plan" High-level Hospital Construction Opening Project of Foshan Fourth People's Hospital[FSSYKF-2020016] ; Foshan Scientific and Technological Innovation Project[FS0AAKJ218-1301-0035]

Immunology

Immunology

WOS:000739057800001

FRONTIERS MEDIA SA

Web of Science

1.Jinan Univ, Zhuhai Inst Translat Med, Zhuhai Peoples Hosp, Zhuhai Hosp, Zhuhai, Peoples R China
2.Southern Univ Sci & Technol, Natl Clin Res Ctr Infect Dis, Guangdong Key Lab Emerging Infect Dis, Shenzhen Third Peoples Hosp, Shenzhen, Peoples R China
3.Jinan Univ, Biomed Translat Res Inst, Fac Med Sci, Guangzhou, Peoples R China
4.Capital Med Univ, Beijing Chest Hosp, Beijing, Peoples R China
5.Guangdong GD Kongming Biotech Ltd, Dept GdT Clin Res & Dev, Guangzhou, Peoples R China
6.Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Chibi Hosp, Chibi, Peoples R China
7.Foshan Fourth Peoples Hosp, Dept TB Control, Foshan, Peoples R China
8.Ctr TB Control Guangdong Prov, Dept TB Control, Guangzhou, Peoples R China

Liang, Juan,Fu, Liang,Li, Man,et al. Allogeneic V gamma 9V delta 2 T-Cell Therapy Promotes Pulmonary Lesion Repair: An Open-Label, Single-Arm Pilot Study in Patients With Multidrug-Resistant Tuberculosis[J]. Frontiers in Immunology,2021,12.

Liang, Juan.,Fu, Liang.,Li, Man.,Chen, Yuyuan.,Wang, Yi.,...&Yin, Zhinan.(2021).Allogeneic V gamma 9V delta 2 T-Cell Therapy Promotes Pulmonary Lesion Repair: An Open-Label, Single-Arm Pilot Study in Patients With Multidrug-Resistant Tuberculosis.Frontiers in Immunology,12.

Liang, Juan,et al."Allogeneic V gamma 9V delta 2 T-Cell Therapy Promotes Pulmonary Lesion Repair: An Open-Label, Single-Arm Pilot Study in Patients With Multidrug-Resistant Tuberculosis".Frontiers in Immunology 12(2021).