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 pat...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(108 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).展开更多
基金This study was funded by the Key Project of Tianjin Second People’s Hospital(No.YS0001)the National Natural Science Foundation of China(No.82002136)the 13th Five-year National Major Project for HIV/AIDS and Hepatitis B Control and Prevention,and the Chinese Ministry of Science and Technology(Nos.2017ZX10202102005004,2018ZX10302104-002)。
文摘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(108 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).
