A pilot clinical trial of HIV antigen-pulsed allogeneic and autologous dendritic cell therapy in HIV-infected patients.
A pilot study was carried out to assess the safety and antigen-presenting properties of allogeneic or autologous dendritic cells (DCs) in six HLA-A2+, HIV-infected patients. Allogeneic DCs obtained from the peripheral blood of HLA-identical, HIV-seronegative siblings were pulsed with recombinant HIV-1 MN gp160 or synthetic peptides corresponding to HLA-A2-restricted cytotoxic epitopes of envelope, Gag, and Pol proteins. The antigen-pulsed cells were infused intravenously six to nine times at monthly intervals and HIV-specific immune responses were monitored. One allogeneic DC recipient with a CD4+ T cell count of 460/mm3 showed increases in envelope-specific CTL- and lymphocyte-proliferative responses, as well as in IFN-gamma and IL-2 production. Another allogeneic DC recipient with a CD4+ T cell count of 434/mm3 also showed an increase in HIV envelope-specific lymphocyte-proliferative responses. A recipient of autologous DCs with a CD4+ T cell count of 730/mm3 showed an increase in peptide-specific lymphocyte-proliferative responses after three infusions. Three other allogeneic DC recipients with CD4+ T cell counts <410/mm3 did not show increases in their HIV-specific immune responses. No clinically significant adverse effects were noted in this study and CD4+ T cell numbers and plasma HIV-1 RNA detected by RT-PCR of all six patients were stable during the study period. Thus, both allogeneic and autologous DC infusions were well tolerated and in patients with normal or near normal CD4+ T cell counts administration of these antigen-pulsed cells enhanced the immune response to HIV. However, since no effect on viral load was observed there was no evidence that this approach provided clinical benefit.
Kundu
S K
SK
Center for AIDS Research at Stanford, Stanford University Medical Center, California 94305-5107, USA. Kundu@leland.stanford.edu
Engleman
E
E
Benike
C
C
Shapero
M H
MH
Dupuis
M
M
van Schooten
W C
WC
Eibl
M
M
Merigan
T C
TC
D002455:Cell Division; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation*; D015488:HIV Antigens / Q000276:immunology*; D019302:HIV Envelope Protein gp160 / Q000276:immunology*; D006679:HIV Seropositivity / Q000628:therapy*; D006801:Humans; D006968:Hypersensitivity, Delayed; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D010865:Pilot Projects; D012367:RNA, Viral; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015488:HIV Antigens; D019302:HIV Envelope Protein gp160; D012367:RNA, Viral; D015847:Interleukin-4; D007371:Interferon-gamma