Immunologic activity and safety of autologous HIV RNA-electroporated dendritic cells in HIV-1 infected patients receiving antiretroviral therapy

被引:84
作者
Routy, Jean-Pierre [1 ,2 ,3 ]
Boulassel, Mohamed-Rachid [2 ]
Yassine-Diab, Bader [3 ,4 ,5 ]
Nicolette, Charles [6 ]
Healey, Don [6 ]
Jain, Renu [6 ]
Landry, Claire [4 ,5 ]
Yegorov, Oleg [3 ,4 ,5 ]
Tcherepanova, Irina [6 ]
Monesmith, Tamara [6 ]
Finke, Lothar [6 ]
Sekaly, Rafick-Pierre [3 ,4 ,5 ]
机构
[1] McGill Univ, McGill Univ Hlth Ctr, Immunodeficiency Serv, Montreal, PQ, Canada
[2] McGill Univ, McGill Univ Hlth Ctr, Div Hematol, Montreal, PQ, Canada
[3] CHU Montreal, Ctr Rech, INSERM, U743, Montreal, PQ H2X 1P1, Canada
[4] CHU Montreal, Hop St Luc, Ctr Rech, Lab Immunol, Montreal, PQ H2X 1P1, Canada
[5] Natl Immune Monitoring Lab, Montreal, PQ, Canada
[6] Argos Therapeut Inc, Durham, NC USA
基金
美国国家卫生研究院;
关键词
HIV; Immunotherapy; Vaccine; Dendritic cells; Acquired immunodeficiency syndrome; TREATMENT INTERRUPTION; VIRUS; CTL; VACCINE; IMMUNOTHERAPY; IMMUNIZATION; MATURATION; INFECTION; VIREMIA; VPR;
D O I
10.1016/j.clim.2009.09.009
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Immunogenicity, manufacturing feasibility, and safety of a novel, autologous dendritic cell (DC)-based immunotherapy (AGS-004) was evaluated in ten human immunodeficiency virus type 1 (HIV-1)-infected adults successfully treated with antiretroviral therapy (ART). Personalized AGS-004 was produced from autologous monocyte-derived DCs electroporated with RNA encoding CD40L and HIV antigens (Gag, Vpr, Rev, and Nef) derived from each subjects' pre-ART plasma. Patients received monthly injections of AGS-004 in combination with ART. AGS-004 was produced within a mean of 6 weeks and yielded 4-12 doses/subject Full or partial HIV-specific proliferative immune responses occurred in 7 of 9 evaluable subjects. Responses were specific for the AGS-004 presented HIV antigens and preferentially targeted CD8(+) T cells. Mild adverse events included flu-like symptoms, fatigue, and injection site reactions. No evidence of autoimmunity, changes in viral load, or significant changes in absolute CD4(+) and CD8(+) T cell counts were observed. This pilot study supports the further clinical investigation of AGS-004. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:140 / 147
页数:8
相关论文
共 39 条
[31]   The Immunosuppressive Properties of the HIV Vpr Protein Are Linked to a Single Highly Conserved Residue, R90 [J].
Tcherepanova, Irina ;
Starr, Aijing ;
Lackford, Brad ;
Adams, Melissa D. ;
Routy, Jean-Pierre ;
Boulassel, Mohamed Rachid ;
Calderhead, David ;
Healey, Don ;
Nicolette, Charles .
PLOS ONE, 2009, 4 (06)
[32]   Ectopic expression of a truncated CD40L protein from synthetic post-transcriptionally capped RNA in dendritic cells induces high levels of IL-12 secretion [J].
Tcherepanova, Irina Y. ;
Adams, Melissa D. ;
Feng, Xiaorong ;
Hinohara, Atsushi ;
Horvatinovich, Joe ;
Calderhead, David ;
Healey, Don ;
Nicolette, Charles A. .
BMC MOLECULAR BIOLOGY, 2008, 9
[33]   Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction [J].
Trautmann, Lydie ;
Janbazian, Loury ;
Chomont, Nicolas ;
Said, Elias A. ;
Gimmig, Sylvain ;
Bessette, Benoit ;
Boulassel, Mohamed-Rachid ;
Delwart, Eric ;
Sepulveda, Homero ;
Balderas, Robert S. ;
Routy, Jean-Pierre ;
Haddad, Elias K. ;
Sekaly, Rafick-Pierre .
NATURE MEDICINE, 2006, 12 (10) :1198-1202
[34]   Reduced protection from simian immunodeficiency virus SIVmac251 infection afforded by memory CD8+ T cells induced by vaccination during CD4+ T-cell deficiency [J].
Vaccari, Monica ;
Mattapallil, Joseph ;
Song, Kaimei ;
Tsai, Wen-Po ;
Hryniewicz, Anna ;
Venzon, David ;
Zanetti, Maurizio ;
Reimann, Keith A. ;
Roederer, Mario ;
Franchini, Genoveffa .
JOURNAL OF VIROLOGY, 2008, 82 (19) :9629-9638
[35]   Efficient stimulation of HIV-1-specific T cells using dendritic cells electroporated with mRNA encoding autologous HIV-1 Gag and Env proteins [J].
Van Gulck, ERA ;
Ponsaerts, P ;
Heyndrickx, L ;
Vereecken, K ;
Moerman, F ;
De Roo, A ;
Colebunders, R ;
Van den Bosch, G ;
Van Bockstaele, DR ;
Van Tendeloo, VFI ;
Allard, S ;
Verrier, B ;
Marañón, C ;
Hoeffel, G ;
Hosmalin, A ;
Berneman, ZN ;
Vanham, G .
BLOOD, 2006, 107 (05) :1818-1827
[36]   Major histocompatibility complex class I-restricted antigen processing and presentation [J].
Van Kaer, L .
TISSUE ANTIGENS, 2002, 60 (01) :1-9
[37]   Production of a Dendritic Cell-Based Vaccine Containing Inactivated Autologous Virus for Therapy of Patients with Chronic Human Immunodeficiency Virus Type 1 Infection [J].
Whiteside, Theresa L. ;
Piazza, Paolo ;
Reiter, Amanda ;
Stanson, Joanna ;
Connolly, Nancy C. ;
Rinaldo, Charles R., Jr. ;
Riddler, Sharon A. .
CLINICAL AND VACCINE IMMUNOLOGY, 2009, 16 (02) :233-240
[38]   HIV-1 viremia prevents the establishment of interleukin 2-producing HIV-specific memory CD4+ T cells endowed with proliferative capacity [J].
Younes, SA ;
Yassine-Diab, B ;
Dumont, AR ;
Boulassel, MR ;
Grossman, Z ;
Routy, JP ;
Sékaly, RP .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 198 (12) :1909-1922
[39]   CD8(+) lymphocyte phenotype and cytokine production in long-term non-progressor and in progressor patients with HIV-1 infection [J].
Zanussi, S ;
Simonelli, C ;
DAndrea, M ;
Caffau, C ;
Clerici, M ;
Tirelli, U ;
dePaoli, P .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 1996, 105 (02) :220-224