PMID- 33958574
OWN - NLM
STAT- MEDLINE
DCOM- 20220323
LR  - 20231111
IS  - 2059-3635 (Electronic)
IS  - 2095-9907 (Print)
IS  - 2059-3635 (Linking)
VI  - 6
IP  - 1
DP  - 2021 May 7
TI  - HLA-mismatched allogeneic adoptive immune therapy in severely immunosuppressed 
      AIDS patients.
PG  - 174
LID - 10.1038/s41392-021-00550-2 [doi]
LID - 174
AB  - Severely immunosuppressed AIDS patients with recurrent opportunistic infections 
      (OIs) 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 OIs 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/mul. Rapid increase in peripheral CD8(+) T-cell count from a 
      median 416.5 to 1206.5 cells/mul 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.
FAU - Xu, Ruonan
AU  - Xu R
AD  - Treatment and Research Center for Infectious Diseases, The Fifth Medical Center, 
      PLA General Hospital, Beijing, China.
FAU - Zhang, Ji-Yuan
AU  - Zhang JY
AD  - Treatment and Research Center for Infectious Diseases, The Fifth Medical Center, 
      PLA General Hospital, Beijing, China.
FAU - Tu, Bo
AU  - Tu B
AD  - Treatment and Research Center for Infectious Diseases, The Fifth Medical Center, 
      PLA General Hospital, Beijing, China.
FAU - Xu, Zhe
AU  - Xu Z
AD  - Treatment and Research Center for Infectious Diseases, The Fifth Medical Center, 
      PLA General Hospital, Beijing, China.
FAU - Huang, Hui-Huang
AU  - Huang HH
AD  - Treatment and Research Center for Infectious Diseases, The Fifth Medical Center, 
      PLA General Hospital, Beijing, China.
FAU - Huang, Lei
AU  - Huang L
AD  - Treatment and Research Center for Infectious Diseases, The Fifth Medical Center, 
      PLA General Hospital, Beijing, China.
FAU - Jiao, Yan-Mei
AU  - Jiao YM
AD  - Treatment and Research Center for Infectious Diseases, The Fifth Medical Center, 
      PLA General Hospital, Beijing, China.
FAU - Yang, Tao
AU  - Yang T
AD  - Treatment and Research Center for Infectious Diseases, The Fifth Medical Center, 
      PLA General Hospital, Beijing, China.
FAU - Zhang, Chao
AU  - Zhang C
AD  - Treatment and Research Center for Infectious Diseases, The Fifth Medical Center, 
      PLA General Hospital, Beijing, China.
FAU - Qin, En-Qiang
AU  - Qin EQ
AD  - Treatment and Research Center for Infectious Diseases, The Fifth Medical Center, 
      PLA General Hospital, Beijing, China.
FAU - Jiang, Tian-Jun
AU  - Jiang TJ
AD  - Treatment and Research Center for Infectious Diseases, The Fifth Medical Center, 
      PLA General Hospital, Beijing, China.
FAU - Xie, Yun-Bo
AU  - Xie YB
AD  - Treatment and Research Center for Infectious Diseases, The Fifth Medical Center, 
      PLA General Hospital, Beijing, China.
FAU - Li, Yuan-Yuan
AU  - Li YY
AD  - Treatment and Research Center for Infectious Diseases, The Fifth Medical Center, 
      PLA General Hospital, Beijing, China.
FAU - Jin, Lei
AU  - Jin L
AD  - Treatment and Research Center for Infectious Diseases, The Fifth Medical Center, 
      PLA General Hospital, Beijing, China.
FAU - Zhou, Chun-Bao
AU  - Zhou CB
AD  - Treatment and Research Center for Infectious Diseases, The Fifth Medical Center, 
      PLA General Hospital, Beijing, China.
FAU - Shi, Ming
AU  - Shi M
AD  - Treatment and Research Center for Infectious Diseases, The Fifth Medical Center, 
      PLA General Hospital, Beijing, China.
FAU - Guo, Mei
AU  - Guo M
AD  - Department of Hematology and Transplantation, The Fifth Medical Center, PLA 
      General Hospital, Beijing, China.
FAU - Ai, Hui-Sheng
AU  - Ai HS
AUID- ORCID: 0000-0001-7002-1702
AD  - Department of Hematology and Transplantation, The Fifth Medical Center, PLA 
      General Hospital, Beijing, China.
FAU - Zhang, Linqi
AU  - Zhang L
AD  - Comprehensive AIDS Research Center, School of Medicine, Tsinghua University, 
      Beijing, China.
FAU - Wang, Fu-Sheng
AU  - Wang FS
AUID- ORCID: 0000-0002-8043-6685
AD  - Treatment and Research Center for Infectious Diseases, The Fifth Medical Center, 
      PLA General Hospital, Beijing, China. fswang302@163.com.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210507
PL  - England
TA  - Signal Transduct Target Ther
JT  - Signal transduction and targeted therapy
JID - 101676423
RN  - 0 (HLA Antigens)
SB  - IM
MH  - *Acquired Immunodeficiency Syndrome/immunology/pathology/therapy
MH  - Adolescent
MH  - *Adoptive Transfer
MH  - Adult
MH  - Allografts
MH  - Female
MH  - HIV-1/*immunology
MH  - HLA Antigens/*immunology
MH  - Humans
MH  - *Leukocytes, Mononuclear/immunology/transplantation
MH  - Male
MH  - Middle Aged
PMC - PMC8102474
COIS- The authors declare no competing interests.
EDAT- 2021/05/08 06:00
MHDA- 2022/03/24 06:00
PMCR- 2021/05/07
CRDT- 2021/05/07 06:35
PHST- 2020/10/15 00:00 [received]
PHST- 2021/02/26 00:00 [accepted]
PHST- 2021/02/04 00:00 [revised]
PHST- 2021/05/07 06:35 [entrez]
PHST- 2021/05/08 06:00 [pubmed]
PHST- 2022/03/24 06:00 [medline]
PHST- 2021/05/07 00:00 [pmc-release]
AID - 10.1038/s41392-021-00550-2 [pii]
AID - 550 [pii]
AID - 10.1038/s41392-021-00550-2 [doi]
PST - epublish
SO  - Signal Transduct Target Ther. 2021 May 7;6(1):174. doi: 
      10.1038/s41392-021-00550-2.