HLA-mismatched allogeneic adoptive immune therapy in severely immunosuppressed AIDS patients  

作　　者：Ruonan Xu Ji-Yuan Zhang Bo Tu Zhe Xu Hui-Huang Huang Lei Huang Yan-Mei Jiao Tao Yang Chao Zhang En-Qiang Qin Tian-Jun Jiang Yun-Bo Xie Yuan-Yuan Li Lei Jin Chun-Bao Zhou Ming Shi Mei Guo Hui-Sheng Ai Linqi Zhang Fu-Sheng Wang 

机构地区：[1]Treatment and Research Center for Infectious Diseases,The Fifth Medical Center,PLA General Hospital,Beijing,China [2]Department of Hematology and Transplantation,The Fifth Medical Center,PLA General Hospital,Beijing,China [3]Comprehensive AIDS Research Center,School of Medicine,Tsinghua University,Beijing,China

出　　处：《Signal Transduction and Targeted Therapy》2021年第6期1780-1787,共8页信号转导与靶向治疗（英文）

基　　金：By grants from National Science and Technology Major Program(2018ZX10302104-002);Innovative Research Group Project of the National Natural Science Foundation of China(81721002);Peking University Clinical Scientist Program supported by"the Fundamental Research Funds for the Central Universities"(BMU2019LCKXJ013).

摘　　要：Severely immunosuppressed AIDS patients with recurrent opportunistic infections(Ols)represent an unmet medical need even in the era of antiretroviral therapy(ART).Here we report the development of a human leukocyte antigen(HLA)-mismatched allogeneic adaptive immune therapy(AAIT)for severely immunosuppressed AIDS patients.Twelve severely immunosuppressed AIDS patients with severe Ols were enrolled in this single-arm study.Qualified donors received subcutaneous recombinant granulocyte-colony-stimulating factor twice daily for 4-5 days to stimulate hematopoiesis.Peripheral blood mononuclear cells were collected from these donors via leukapheresis and transfused into the coupled patients.Clinical,immunological,and virological parameters were monitored during a 12-month follow-up period.We found AAIT combined with ART was safe and well-tolerated at the examined doses and transfusion regimen in all 12 patients.Improvements in clinical symptoms were evident throughout the study period.All patients exhibited a steady increase of peripheral CD4^(+)T cells from a median 10.5 to 207.5 cells/μl.Rapid increase in peripheral CD8^(+)T-cell count from a median 416.5 to 1206.5 cells/μl was found in the first 90 days since initiation of AAIT.In addition,their inflammatory cytokine levels and HIV RNA viral load decreased.A short-term microchimerism with donor cells was found.There were no adverse events associated with graft-versus-host disease throughout the study period.Overall,AAIT treatment was safe,and might help severely immunosuppressed AIDS patients to achieve a better immune restoration.A further clinical trial with control is necessary to confirm the efficacy of AAIT medication.

关 键 词：PATIENTS doses TRANSFUSION 

分 类 号：R512.91[医药卫生—内科学]