Safety and efficacy of allogeneic natural killer cell immunotherapy on human immunodeficiency virus type 1 immunological non-responders: a brief report.
10.1097/CM9.0000000000001189
- Author:
Huan XIA
1
;
Yin WANG
2
;
Hua-Li SUN
3
;
Li-Ying GAO
1
;
Yu CAO
4
;
Silvere D ZAONGO
1
;
Rong-Nan ZENG
4
;
Hao WU
5
;
Ming-Jie ZHANG
6
;
Ping MA
1
Author Information
1. Department of Infectious Diseases, Nankai University Second People's Hospital, Tianjin 300192, China.
2. Department of Infectious Diseases, Public Health Clinical Center of Chengdu, Chengdu, Sichuan 610066, China.
3. Department of Infectious Diseases, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, China.
4. Tianjin Institute of Hepatology, Nankai University Second People's Hospital, Tianjin 300192, China.
5. Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China.
6. HANK Bioengineering Co., Ltd., Shenzhen, Guangdong 518000, China.
- Publication Type:Randomized Controlled Trial
- MeSH:
CD4 Lymphocyte Count;
HIV Infections/therapy*;
HIV-1;
Hematopoietic Stem Cell Transplantation;
Humans;
Immunotherapy;
Killer Cells, Natural;
Prospective Studies;
Viral Load
- From:
Chinese Medical Journal
2020;133(23):2803-2807
- CountryChina
- Language:English
-
Abstract:
BACKGROUND:Allogeneic natural killer (NK) cell immunotherapy is recognized as a promising anti-tumor strategy, but whether it plays a role in poor CD4 recovery among human immunodeficiency virus type 1 (HIV-1) infected patients is unknown. This study aimed to investigate the safety and effectiveness of allogeneic NK cells immunotherapy on HIV-1 immunological non-responders (INRs) receiving antiretroviral therapy (ART).
METHODS:From February to April 2018, a prospective, randomized, controlled, open-label clinical trial, which enrolled 20 HIV-1 INRs following specific inclusion criteria, was conducted at Nankai University Second People's Hospital. Participants were randomly allocated (simple randomization 1:1) to either the combined treatment (NK + ART) group (n = 10) or the control (ART) group (n = 10). The allogenic highly activated NK cells from killer cell immunoglobulin-like receptor (KIR)/human leukocyte antigen (HLA)-Cw mismatched healthy donor were prepared (10 cells in each injection) and intravenously infused to each recruited patient of NK+ART group in three courses. Key immune parameters (CD4 count, CD8 count, CD4/CD8 ratio), laboratory tests (count of blood cells, biochemistry panel) and symptoms at baseline and at month 1, 3, 6, 9, 12, and 24 were measured/collected to analyze the safety and efficacy of the therapy. Comparisons were between the seven time-points of both groups using repeated measurement analysis of variance (ANOVA) test. Generalized estimating equations (GEE) model was performed to evaluate the overall effect of the NK+ART group vs. the ART group.
RESULTS:From baseline to 24 months, we noted a mean CD4 count augmentation (139 to 243 cells/μL) in the NK + ART group and (144 to 176 cells/μL) in the ART group (difference, 67; 95% CI, 10 to 124; P = 0.024). Our estimations revealed that NK+ART group could improve CD4 level (β = 54.59, P = 0.006) and CD8 level (β = 322.47, P = 0.010) on average among the six measurements compared with the ART group. Only two (2/10, 20%) participants in the NK+ART group developed a transient mild fever after the first course.
CONCLUSIONS:This preliminary study informs that HIV-1 INRs, allogenic NK cells immunotherapy is safe and could significantly improve CD4 recovery but not CD4/CD8 ratio. The practical effects, however, need long-term follow-up observations. Further study on the potential underlying mechanism is warranted. REGISTRATION INFO:: www.chictr.org.cn/showproj.aspx?proj=34912 (No. ChiCTR1900020634).
